From the Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, University of Manchester, M13 9PT Manchester, United Kingdom
Migration of myogenic cells from the somites and
their subsequent fusion to myotubes are key steps during skeletal
muscle development. Continuous interaction of the cells with the
neighborhood most likely triggers all events necessary to induce the
genetic programs for differentiation, migration, and fusion into
multinucleated myotubes. Likewise, it is well recognized that the
function and the maintenance of tissue integrity are dependent on
specific interactions of cells with the surrounding extracellular
matrix. Transmembrane receptors are involved in polymerization and
assembly of the matrix (1, 2) and in addition provide both a mechanical link to the cytoskeleton and a means of transducing signals from the
extracellular matrix to the nucleus (3, 4). In skeletal muscle two
major types of extracellular-cytoskeletal linkages exist at the cell
plasma membrane. Numerous studies over the past decade have addressed
the function of the dystrophin-glycoprotein complex
(DGC).1 Insights into the
biological significance of integrin receptors for skeletal muscle
development and function have been gained more recently, largely by
gene targeting approaches and analyses of human diseases caused by
integrin mutations. This review will therefore focus mainly on recent
advances in understanding of the function of integrins in skeletal muscle.
Integrins form the major family of cell surface adhesion
receptors, mediating both cell-cell and cell-matrix interactions. They
are heterodimeric, transmembrane glycoproteins consisting of an So far, most conclusions about function and expression of integrins in
vertebrate skeletal muscle have been drawn from combined studies in
human, rat, mouse, chicken, and quail, mainly utilizing in
vitro approaches. It is difficult from these studies to evaluate the precise function of integrins at the tissue level, as some integrins have only been detected in one species but not in others (7).
Of the 12 current members of the
INTRODUCTION
TOP
INTRODUCTION
Integrins in Skeletal Muscle
Integrins in Skeletal Muscle...
Conclusions and Perspectives
REFERENCES
Integrins in Skeletal Muscle
TOP
INTRODUCTION
Integrins in Skeletal Muscle
Integrins in Skeletal Muscle...
Conclusions and Perspectives
REFERENCES
and
a
chain that are non-covalently associated (5). To date, 18
and
8
chains have been identified, and these combine in a restricted
manner to form at least 24 different dimers (6). Integrin diversity is
increased still further through the expression of intra- and
extracellular splice variants for several subchains. Among these, the
1 integrin family forms the largest group of receptors
for extracellular matrix proteins.
1 integrin family, a subset has been shown convincingly to be expressed in mammalian at focal contacts, costameres, neuromuscular (NMJ) and
myotendinous junctions (MTJ), or the sarcolemmal membrane during
either muscle development or in the adult (Fig.
1).
View larger version (18K):
[in a new window]
Fig. 1.
Schematic presentation of integrin expression
in mouse skeletal muscle. In migrating myoblasts, the
4-
7,
v, and
1A subunits are present. During secondary myogenesis at
late embryonic and early postnatal stages the indicated subunits are
present. Note that the
1A variant is replaced by
1D. In the adult, only
7
1D
is found at the sarcolemma and at MTJs, whereas at NMJs the
7 chain along with
3 and
v
subunits is present.
Integrins in In Vitro Muscle Differentiation--
Studies
performed in avian have indicated that 1
integrins are involved in cell migration from the somite (8) and
terminal differentiation of myoblasts into myotubes (9). In
vitro studies in avian and rodent species imply that the
4 integrins, containing either the
1 or
7 subunit, and
v,
5
1,
6
1, and
7
1 integrins are the major players in
muscle differentiation. These integrin chains are readily detected in
myoblasts. The
4 integrins were thought to be of
particular importance providing the major cell-cell contact for myotube
formation during secondary myogenesis through a heterophilic
interaction with the counter-receptor VCAM-1 (10). However, chimeric
mice with a high percentage of
4-deficient embryonic
stem (ES) cells formed normal muscle (11). These data, together
with the demonstration that, in vitro,
4-deficient myoblasts can form myotubes strongly
suggests that
4-containing integrins are not required to
establish the cell-cell contacts necessary for myoblast fusion
(11).
Whereas 5
1 is the classical fibronectin
receptor, both
6
1 and
7
1 are exclusive laminin receptors.
5
1 and
6
1
are widely expressed and down-regulated after myotube formation
(12-14), whereas
7
1 is mainly restricted
to skeletal and cardiac muscle and strongly up-regulated upon myoblast
fusion (15, 16). The role of
5
1 and
6
1 in muscle development and the reason
they coexist at the myoblast stage as ligand-opposing receptors is not
yet well defined. Elegant studies by Sastry et al. (17), however, suggested distinct functions for both integrins.
Overexpression of the
5 subunit in primary quail
myoblasts maintained them in a proliferative phase, whereas ectopically
expressed
6
1 induced myoblast
differentiation (17). Given the switch in the muscle cell environment
from a fibronectin-rich matrix into a laminin-containing basement
membrane with the onset of terminal differentiation (18), these data
suggested a fine-tuned regulation of differentiation and matrix
assembly via these two integrin receptors. However, no obvious defects
in muscle development have been reported either in mice with a targeted
deletion of the
6 subunit (19) or in myoblasts devoid of
5
1 that efficiently differentiated into myotubes (20).
Various results have implicated 7
1 as the
crucial receptor for myoblast migration (21-23), and its strong
up-regulation in terminally differentiated myotubes further suggested a
functional role in this process. Yet, as with other integrin
chain-null mice, skeletal muscle develops normally in the absence of
7
1 (24).
The apparently normal myogenesis in integrin chain-null mice could
be explained by redundancy or overlap in function (25) because integrin
1-inhibiting antibodies, which disrupt the function of
all integrins concurrently, perturbed myotube formation in vitro (9). However, a critical role for integrins in muscle development became questionable, when it was demonstrated that skeletal
muscle in chimeric mice derived from
1-null ES cells formed normally in vivo, and
1 homozygous
mutant myoblasts were shown to be fusion-competent, although
differentiation of
1-null ES cells into myotubes was
delayed (26, 27). These data supported the view that early muscle
development is regulated mainly by transcription and growth factors
(28), although integrins could be one of the downstream targets. The
availability of conditional skeletal muscle-specific
1-integrin knock-out mice, however, has now shed new
light on this field of research. Mice lacking
1 integrin
specifically in muscle die immediately after birth with only poorly
developed muscle fibers.2 At
first glance, these data are at odds with earlier results, suggesting
that
1 integrins were not required for myogenesis (26,
27). However, upon closer examination it is apparent that both models
differ significantly. In the conditional
1 integrin-null mice, all myoblasts lack
1 integrins, whereas in the
chimeric mice,
1-deficient cells are interspersed in a
mosaic pattern with wild-type cells. The tight contact between
wild-type and mutant cells may commit
1-deficient
myoblasts to differentiation, or alternatively, wild-type cells may
secrete soluble factors in a
1
integrin-dependent manner. This could be sufficient to induce the genetic program in the neighboring
1
knock-out cells. Obviously, the conclusions drawn about individual
subunits based on the analysis in chimeric animals have to be
reconsidered in view of the impact caused by the environment. Further
work will undoubtedly yield important insights into the role of
1 integrins for skeletal muscle differentiation, and the
race is on again to determine whether an individual or a combination of
integrins underlies the phenotype observed in
1-deficient skeletal muscle.
Integrins in Adult Skeletal Muscle--
Muscle fibers are
surrounded by a basement membrane, composed of the main constituents
laminin, collagen IV, the heparan sulfate proteoglycan perlecan, and
nidogen-1 (29). Most likely, cell-matrix contact is predominantly
maintained through the interaction of muscle cell transmembrane
receptors and laminin, the major cell-adhesive protein found in
basement membranes. Laminin is a family of ubiquitously expressed
heterotrimeric proteins, composed of an , a
, and a
chain.
The current identification of 14 distinct laminin isoforms is mainly
due to the existence of five
(
1-
5),
three
(
1-
3), and three
(
1-
3) chains (30). In skeletal muscle
the
2,
4, and
5 chains
have been identified (31-33). The
4 and
5 chains, however, disappear perinatally from the
sarcolemmal membrane and become restricted to the NMJ and blood vessels
(31-33). Laminin-2 (
2
1
1) and laminin-4 (
2
2
1) are
therefore the major laminin isoforms present throughout muscle
development and in the adult, providing the intimate contact between
basement membranes and the muscle fibers both at junctional (NMJ and
MTJ) and non-junctional areas (34).
Accordingly, laminin receptors are thought to play pivotal roles for
skeletal muscle function and integrity. All laminin isoforms detected
in skeletal muscle are recognized by 3
1,
6
1, and
7
1
(35-37). Yet, only two laminin receptor systems in the mature skeletal
muscle have been shown to be present ubiquitously, namely the DGC and
7
1 integrin. Both are thought to connect
the extracellular matrix and the cytoskeleton and thus provide the
necessary muscle stability during contraction. Mutations in
the dystrophin gene cause Duchenne or Becker muscular
dystrophies (38), and genes encoding components of the DGC have been
shown to be mutated in various forms of muscular dystrophies (39,
40).
7
1 integrin is the major if not the
exclusive integrin receptor found in adult skeletal muscle. It is
highly enriched at MTJs (41) and is localized at the NMJ together with
3- and
v-containing integrins (42). There
have been some arguments that the
10
1 and
11
1 integrins localize at the MTJ in
adult muscle. Further analysis is still required to clarify whether these integrins are expressed by muscle or alternatively by tendon as
their ligand specificity would suggest (43).
Structural and Functional Features of
7
1--
The
7
1 subunit was originally identified from
myoblasts and melanoma cells as laminin-1-binding (
1
1
1)
integrin (44 ,45). The diversity of the
7
1 integrin is further increased due to the occurrence of alternative mRNA splice variants for both the extracellular and cytoplasmic domains. The major variants in the extracellular domain are the mutually exclusive X1 and X2 domains located between domains III and IV of the conserved repeat motifs, common to all integrins (46, 47), and the A and B variants for the
cytoplasmic domain (46, 48). In addition, some minor extracellular
variants have been identified (49-51), and in rat a third cytoplasmic
C variant was described (15), which, however, is not found in the human
and murine ITGA7 genes (50).
The spatiotemporal expression of the extracellular and the cytoplasmic
variants are developmentally regulated. 7B is expressed in proliferating myoblasts, whereas the A variant is induced only upon
terminal differentiation (46, 48). Both forms have been immunolocalized
to the NMJ and MTJ in the adult muscle, whereas at the sarcolemma the
current data are not conclusive. The rat-specific cytoplasmic C variant
was postulated to be the exclusive splice form found at the sarcolemma
(15). In mouse and human, however,
7B was detected along
the muscle fiber membrane (52-54) and in accordance with our data
seems to be the predominant splice form found at the sarcolemmal
membrane.3
In contrast to the intracellular domains, only the extracellular X2
variant is found in adult skeletal muscle, whereas X1 and X2 are
simultaneously expressed throughout muscle development. Initial data
suggested that the 7 subunit is restricted to skeletal and cardiac muscle (55). The
7B subunit, however, is
ubiquitously expressed as it has been detected in smooth muscle,
neuronal, and trophoblast cells and a variety of tissues (48, 56-58).
Among the possible splice variants only those containing the
cytoplasmic A variant appear therefore to be skeletal
muscle-specific.
There is still much to learn about the specificities of the
7 integrin splice variants. Although integrin
cytoplasmic domains are generally accepted to be involved in signaling
events, so far no conclusive evidence has been provided that
functionally distinguishes the A and the B variants of the
7 subunit in terms of cell migration, proliferation, or
matrix assembly (16, 59). Interestingly, however, cell adhesion and
ligand-binding studies of transfected cells and recombinant soluble
7
1 suggest that the extracellular X1/X2
variants are not identical in function. Ziober et al. (60)
showed that whereas
7X2 is constitutively active in
binding to laminin-1, the X1 variant only becomes adhesive after
treatment with an activating
1 antibody. In line with
these data, soluble
7X2
1 bound to
laminin-1, whereas in the presence of X1,
7
1 preferentially interacted with
laminin-8 (
4
1
1) (37). Both extracellular splice variants,
however, showed the same binding activity to laminin-2. As the laminin
4 chain is only present during muscle development and up-regulated
in muscle regeneration (31, 61), it is tempting to speculate that X1- or X2-containing
7
1 might have subtly
distinct functions in these processes.
Cytoplasmic variants have also been described for the 1
subunit. The major forms represent
1A and
1D, whereas
1B and
1C are
minor forms and only exist in human.
1A is ubiquitously
expressed, with the exception of skeletal and cardiac muscle, where it
is replaced by the homologous
1D variant. In skeletal
muscle the
1D subunit exclusively associates with the
7 chain. Upon expression in integrin
1-deficient cells,
1D caused multiple
changes in the cellular morphology and strengthened the link between
the cytoskeleton and the extracellular matrix as compared with
1A (62), a finding that is in accordance with the strong
force transmission occurring in skeletal muscle. Further analysis
suggested
1D to be involved in the inhibition of
myoblast proliferation (63). Mice with a replacement of
1D by
1A, however, showed normal muscle
function and histology, and only a mild disturbance of cardiac function
was found (64). The significance of
7 in association
with
1D remains therefore open at present.
![]() |
Integrins in Skeletal Muscle Diseases |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
Muscular dystrophies are a group of heterogeneous inherited
muscle-wasting diseases. Linked genes identified to date are highly diverse and comprise extracellular matrix proteins, transmembrane and
associated proteins, proteases, enzymes, and cytoplasmic and nuclear
membrane proteins (40, 65, 66). All interfere at certain stages with
normal muscle structure and function, finally leading to similar
pathological changes. The currently best accepted model underlying the
etiology of the disease predicts that any disturbance of the molecular
link between the extracellular matrix and the cytoskeleton results in
impaired muscle stability. This theory arose when the first
loss-of-function mutations in dystrophin were identified as the cause
of DMD (66). Dystrophin binds to F-actin and with its C-terminal domain
to -dystroglycan, which in turn interacts with the laminin-binding
-dystroglycan (67). Furthermore, mutations within the laminin
2
chain result in severe forms of congenital muscular dystrophy (CMD)
both in human and the corresponding mouse model
dy/dy (68, 69).
Muscular Dystrophies Caused by Integrins--
Integrins
provide a similar link between the cytoskeleton and the extracellular
matrix as the DGC and were therefore strong candidate genes for
unclassified forms of muscular dystrophies. Indeed, mice carrying an
inactivated 7 integrin gene were shown to develop a mild
but progressive muscular dystrophy soon after birth (24). The
histological features characteristic for muscular dystrophies were
restricted to the deeply located soleus muscle and the diaphragm,
whereas the muscle fibers in all other muscles were unaffected. In the
meantime, human patients have been identified with a primary integrin
7 deficiency, resulting from a 21-bp insertion due to a
splice site mutation or deletions leading to frameshifts (53). The
disease was apparent from birth with delayed motor milestones in the
following years of age and was accordingly classified as congenital
myopathy. Interestingly, no mutations in the coding region could be
identified in one patient with a lack of
7 integrin
staining and low levels of transcript (53). This implies a mutation in
the promoter region or in a regulatory element of the gene, and its
identification may yield valuable insight into the transcriptional
regulation of the ITGA7 gene. The phenotypes observed in
mouse and human are highly similar. Neither myofiber necrosis nor
muscle fiber regeneration was predominant, and human muscle biopsies
revealed only a mild fiber size variation. The staining pattern for the
laminin
2 chain and components of the DGC were unaltered (24, 53).
The mild histopathology is in contrast to the severity of the disease
in human species. The integrin
7-deficient mice,
however, might in part explain the etiology of the disease, as muscles
are readily accessible. MTJs, the primary site of force transmission
between the muscle and the tendon, were severely destructed in all
muscles in these mice. The majority had lost their digit-like
extensions, and the sarcomer was retracted from the muscle membrane,
suggesting an impairment of function of the MTJ (24, 70). A similar
role of integrins for muscle integrity has been reported for two
Drosophila PS integrin mutations, myospheroid
(
PS) and inflated (
PS2). In both cases the muscles
appeared to develop normally with correctly formed attachment sites,
but on contraction the sarcomers detached from the cell membrane (71,
72). Based on these animal models, it is highly likely that the same
consequences occur in human patients and might explain the muscle
weakness despite the rather mild myofiber damage.
So far no other human skeletal muscle diseases have been linked
to mutations in integrin genes. Yet, another candidate gene for an
unclassified CMD is the integrin 5 subunit. The analysis of integrin
5
/
chimeric mice with a high
contribution of
5 homozygous mutant cells in skeletal
muscle revealed the characteristics for muscular dystrophies (20).
Intriguingly, these changes were already evident at late embryonic
stages and suggest that
5
1 is more
important than
7
1 during muscle
maturation. It is also worthwhile to note that
5
1 is a classical fibronectin receptor favoring the idea that a fine balance between fibronectin and laminin-rich matrices and their receptors is critical for muscle integrity at late embryonic and early postnatal stages. As integrin
5 deficiency leads to embryonic lethality at
midgestation due to mesodermal defects in mice (73), it will be
interesting whether mutations in the ITGA5 gene, which
interfere with ligand binding or result in a hypomorph due to
promoter/enhancer mutations, can be identified.
Secondary Reduction of 7
1 in Muscular
Dystrophies--
The demonstration that mutations affecting
7
1 caused muscular dystrophy led to a
broad investigation about its expression pattern in other myopathies of
known and unknown origin. At most, only minor changes in expression
have been noted with the exception of severe forms of CMD linked to
mutations in the laminin
2 chain. Concomitant with the loss or
defective expression of the laminin-2 and -4 isoforms in the muscle
basement membrane, several independent investigations of diseased human
and murine muscle demonstrated a reduction for the integrin
7 and
1D subunits as a secondary consequence, whereas components of the DGC appeared unaffected (54, 74,
75). The same was also observed in Fukuyama CMD and muscle-eye-brain
disease, for which a secondary reduction of the laminin
2 chain was
reported (75). These findings underline that laminin
2-containing
isoforms are indeed the major ligands for
7
1 integrin at the muscle membrane.
Relationship of 7
1 Integrin and the
DGC--
The critical presence of
7
1
integrin and the DGC to maintain muscle integrity raised the question
as to whether both can compensate for each other. A higher staining
intensity for
7
1 in sections of DMD
patients and the corresponding mouse model, mdx, has been
observed (54, 74, 75), although it is still controversial whether this
is due to increased transcription (53, 74). In contrast, components of
the DGC were unchanged in
7 deficiency (24, 53, 54).
Further, both complexes differ in that
7
1
integrin and the DGC are essential for MTJ stability and the lateral
integrity of the muscle fiber, respectively (70, 76). This supports the
notion that both are independently controlled receptor systems and that
the underlying mechanisms leading to the disease are different.
The presence of either complex, however, is essential, as
double-mutant mice lacking dystrophin and
7
1 develop a severe dystrophy and die
within 4 weeks after birth.3
7
1 as a Therapeutic Tool for
DMD--
DMD is a severe X-linked disease and affects about 1 in 3000 males. Over the past years a major effort has been put into therapeutic strategies to ameliorate the disease. Various approaches tried to
restore dystrophin in skeletal muscle by myoblast or virally mediated
gene transfer (77). The most promising approach, however, dealt with
the constitutive up-regulation of utrophin, a dystrophin homologue,
which had been shown to compensate in mdx mice for the loss
of dystrophin (66). As
7
1 showed
increased staining intensities in DMD patients and mdx mice,
Burkin et al. (78) tested the idea that overexpression of
the
7 subunit in dystrophin/utrophin double-mutant mice
might restore muscle integrity. Although degeneration, as expressed by
the percentage of muscle fibers with centrally located nuclei, was
similar in the double mutants and those overexpressing the
7 subunit, life span increased 3-fold in conjunction
with higher mobility upon overexpression of the
7
subunit (78). The high degree of de- and regeneration supports the view
that
7
1 and the DGC complex are
distinctive receptors but that increased amounts of
7
1 are capable of stabilizing muscle
function and ameliorating the dystrophin-deficient phenotype. More work
is needed to investigate this promising approach for DMD therapy.
![]() |
Conclusions and Perspectives |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
The discoveries made in recent years emphasize that integrins are
indispensable both for muscle development and muscle function in the
adult and not redundant to the DGC. Although much progress has been
made by identifying muscular dystrophies caused by loss-of-function mutations in 5
1 and
7
1 integrins, our understanding about the
underlying mechanisms is still very incomplete, and several key
questions remain open (Fig. 2). For
example, through which linker proteins are both integrins connected to
the actin cytoskeleton? Which signaling cascades are associated with
the receptors in skeletal muscle? The answers to these questions will
not only elucidate the pathogenesis of the disease but may also uncover new strategies to improve the concept for therapeutic approaches of DMD
patients by integrins.
|
![]() |
ACKNOWLEDGEMENTS |
---|
Many thanks to Drs. D. Gullberg and R. Boot- Handford for critical reading of the manuscript and helpful comments.
![]() |
FOOTNOTES |
---|
* This minireview will be reprinted in the 2003 Minireview Compendium, which will be available in January, 2004. This is the third article of four in the "Skeletal Muscle Basement Membrane-Sarcolemma-Cytoskeleton Interaction Minireview Series."
To whom correspondence should be addressed: Wellcome Trust Centre
for Cell-Matrix Research, University of Manchester, 3.239 Stopford
Bldg., Oxford Rd., Manchester M13 9PT, UK. Tel.: 44-161-275-5246; Fax:
44-161-275-3915; E-mail: Ulrike.Mayer@man.ac.uk.
Published, JBC Papers in Press, January 29, 2003, DOI 10.1074/jbc.R200022200
2 M. Schwander and U. Müller, personal communication.
3 M. Willem and U. Mayer, unpublished results.
![]() |
ABBREVIATIONS |
---|
The abbreviations used are: DGC, dystrophin glycoprotein complex; CMD, congenital muscular dystrophy; DMD, Duchenne muscular dystrophy; MTJ, myotendinous junction; NMJ, neuromuscular junction; ES, embryonic stem.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
1. | Henry, M. D., and Campbell, K. P. (1998) Cell 95, 859-870[Medline] [Order article via Infotrieve] |
2. | Sasaki, T., Forsberg, E., Bloch, W., Addicks, K., Fässler, R., and Timpl, R. (1998) Exp. Cell Res. 238, 70-81[CrossRef][Medline] [Order article via Infotrieve] |
3. | Sastry, S. K., and Horwitz, A. F. (1993) Curr. Opin. Cell Biol. 5, 819-831[Medline] [Order article via Infotrieve] |
4. | Schwartz, M. A. (2001) Trends Cell Biol. 11, 466-470[CrossRef][Medline] [Order article via Infotrieve] |
5. | Hynes, R. O. (1992) Cell 69, 11-25[Medline] [Order article via Infotrieve] |
6. | van der Flier, A., and Sonnenberg, A. (2001) Cell Tissue Res. 305, 285-298[CrossRef][Medline] [Order article via Infotrieve] |
7. | Mcdonald, K. A., Horwitz, A. F., and Knudsen, K. A. (1995) Semin. Dev. Biol. 6, 105-116[CrossRef] |
8. | Jaffredo, T., Horwitz, A. F., Buck, C. A., Rong, P. M., and Dieterlen-Lievre, F. (1988) Development 103, 431-446[Abstract] |
9. | Menko, A. S., and Boettiger, D. (1987) Cell 51, 51-57[Medline] [Order article via Infotrieve] |
10. | Rosen, G. D., Sanes, J. R., LaChance, R., Cunningham, J. M., Roman, J., and Dean, D. C. (1992) Cell 69, 1107-1119[Medline] [Order article via Infotrieve] |
11. | Yang, J. T., Rando, T. A., Mohler, W. A., Rayburn, H., Blau, H. M., and Hynes, R. O. (1996) J. Cell Biol. 135, 829-835[Abstract] |
12. | Bronner-Fraser, M., Artinger, M., Muschler, J., and Horwitz, A. F. (1992) Development 115, 197-211[Abstract] |
13. | Blaschuk, K. L., and Holland, P. C. (1994) Dev. Biol. 164, 475-483[CrossRef][Medline] [Order article via Infotrieve] |
14. | Boettiger, D., Enomoto-Iwamoto, M., Yoon, H. Y., Hofer, U., Menko, A. S., and Chiquet-Ehrismann, R. (1995) Dev. Biol. 169, 261-272[CrossRef][Medline] [Order article via Infotrieve] |
15. |
Song, W. K.,
Wang, W.,
Sato, H.,
Bielser, D. A.,
and Kaufman, S. J.
(1993)
J. Cell Sci.
106,
1139-1152 |
16. |
Yao, C. C.,
Ziober, B. L.,
Sutherland, A. E.,
Mendrick, D. L.,
and Kramer, R. H.
(1996)
J. Cell Sci.
109,
3139-3150 |
17. | Sastry, S. K., Lakonishok, M., Thomas, D. A., Muschler, J., and Horwitz, A. F. (1996) J. Cell Biol. 133, 169-184[Abstract] |
18. | Kühl, U., Öcalan, M., Timpl, R., and von der Mark, K. (1986) Dev. Biol. 117, 628-635[Medline] [Order article via Infotrieve] |
19. | Georges-Labouesse, E., Messaddeq, N., Yehia, G., Cadalbert, L., Dierich, A., and Le Meur, M. (1996) Nat. Genet. 13, 370-373[Medline] [Order article via Infotrieve] |
20. |
Taverna, D.,
Disatnik, M. H.,
Rayburn, H.,
Bronson, R. T.,
Yang, J.,
Rando, T. A.,
and Hynes, R. O.
(1998)
J. Cell Biol.
143,
849-859 |
21. |
Echtermeyer, F.,
Schöber, S.,
Pöschl, E.,
von der Mark, H.,
and von der Mark, K.
(1996)
J. Biol. Chem.
271,
2071-2075 |
22. |
Yao, C. C.,
Ziober, B. L.,
Squillace, R. M.,
and Kramer, R. H.
(1996)
J. Biol. Chem.
271,
25598-25603 |
23. | Crawley, S., Farrell, E. M., Wang, W., Gu, M., Huang, H. Y., Huynh, V., Hodges, B. L., Cooper, D. N., and Kaufman, S. J. (1997) Exp. Cell Res. 235, 274-286[CrossRef][Medline] [Order article via Infotrieve] |
24. | Mayer, U., Saher, G., Fässler, R., Bornemann, A., Echtermeyer, F., von der Mark, H., Miosge, N., Pöschl, E., and von der Mark, K. (1997) Nat. Genet. 17, 318-323[Medline] [Order article via Infotrieve] |
25. | Hynes, R. O. (1996) Dev. Biol. 180, 402-412[CrossRef][Medline] [Order article via Infotrieve] |
26. | Fässler, R., and Meyer, M. (1995) Genes Dev. 9, 1896-1908[Abstract] |
27. |
Hirsch, E.,
Lohikangas, L.,
Gullberg, D.,
Johansson, S.,
and Fässler, R.
(1998)
J. Cell Sci.
111,
2397-2409 |
28. | Arnold, H. H., and Braun, T. (2000) Curr. Top. Dev. Biol. 48, 129-164[Medline] [Order article via Infotrieve] |
29. | Timpl, R., and Brown, J. C. (1996) Bioessays 18, 123-132[Medline] [Order article via Infotrieve] |
30. |
Libby, R. T.,
Champliaud, M. F.,
Claudepierre, T.,
Xu, Y.,
Gibbons, E. P.,
Koch, M.,
Burgeson, R. E.,
Hunter, D. D.,
and Brunken, W. J.
(2000)
J. Neurosci.
20,
6517-6528 |
31. |
Patton, B. L.,
Miner, J. H.,
Chiu, A. Y.,
and Sanes, J. R.
(1997)
J. Cell Biol.
139,
1507-1521 |
32. | Ringelmann, B., Roder, C., Hallmann, R., Maley, M., Davies, M., Grounds, M., and Sorokin, L. (1999) Exp. Cell Res. 246, 165-182[CrossRef][Medline] [Order article via Infotrieve] |
33. | Sorokin, L. M., Pausch, F., Frieser, M., Kröger, S., Ohage, E., and Deutzmann, R. (1997) Dev. Biol. 189, 285-300[CrossRef][Medline] [Order article via Infotrieve] |
34. | Gullberg, D., Tiger, C. F., and Velling, T. (1999) Cell Mol. Life Sci. 56, 442-460[Medline] [Order article via Infotrieve] |
35. |
Fujiwara, H.,
Kikkawa, Y.,
Sanzen, N.,
and Sekiguchi, K.
(2001)
J. Biol. Chem.
276,
17550-17558 |
36. |
Kikkawa, Y.,
Sanzen, N.,
Fujiwara, H.,
Sonnenberg, A.,
and Sekiguchi, K.
(2000)
J. Cell Sci.
113,
869-876 |
37. |
von der Mark, H.,
Williams, I.,
Wendler, O.,
Sorokin, L.,
von der Mark, K.,
and Pöschl, E.
(2002)
J. Biol. Chem.
277,
6012-6016 |
38. | Hoffman, E. P., and Kunkel, L. M. (1989) Neuron 2, 1019-1029[Medline] [Order article via Infotrieve] |
39. | Ozawa, E., Noguchi, S., Mizuno, Y., Hagiwara, Y., and Yoshida, M. (1998) Muscle Nerve 21, 421-438[CrossRef][Medline] [Order article via Infotrieve] |
40. | Durbeej, M., and Campbell, K. P. (2002) Curr. Opin. Genet. Dev. 12, 349-361[CrossRef][Medline] [Order article via Infotrieve] |
41. |
Bao, Z. Z.,
Lakonishok, M.,
Kaufman, S.,
and Horwitz, A. F.
(1993)
J. Cell Sci.
106,
579-589 |
42. | Martin, P. T., Kaufman, S. J., Kramer, R. H., and Sanes, J. R. (1996) Dev. Biol. 174, 125-139[CrossRef][Medline] [Order article via Infotrieve] |
43. | Gullberg, D. E., and Lundgren-Akerlund, E. (2002) Prog. Histochem. Cytochem. 37, 3-54[Medline] [Order article via Infotrieve] |
44. |
von der Mark, H.,
Dürr, J.,
Sonnenberg, A.,
von der Mark, K.,
Deutzmann, R.,
and Goodman, S. L.
(1991)
J. Biol. Chem.
266,
23593-23601 |
45. | Kramer, R. H., Vu, M. P., Cheng, Y. F., Ramos, D. M., Timpl, R., and Waleh, N. (1991) Cell Regul. 2, 805-817[Medline] [Order article via Infotrieve] |
46. |
Ziober, B. L.,
Vu, M. P.,
Waleh, N.,
Crawford, J.,
Lin, C. S.,
and Kramer, R. H.
(1993)
J. Biol. Chem.
268,
26773-26783 |
47. |
Springer, T. A.
(1997)
Proc. Natl. Acad. Sci. U. S. A.
94,
65-72 |
48. |
Collo, G.,
Starr, L.,
and Quaranta, V.
(1993)
J. Biol. Chem.
268,
19019-19024 |
49. | Leung, E., Lim, S. P., Berg, R., Yang, Y., Ni, J., Wang, S. X., and Krissansen, G. W. (1998) Biochem. Biophys. Res. Commun. 243, 317-325[CrossRef][Medline] [Order article via Infotrieve] |
50. | Vignier, N., Moghadaszadeh, B., Gary, F., Beckmann, J., Mayer, U., and Guicheney, P. (1999) Biochem. Biophys. Res. Commun. 260, 357-364[CrossRef][Medline] [Order article via Infotrieve] |
51. |
Pegoraro, E.,
Cepollaro, F.,
Prandini, P.,
Marin, A.,
Fanin, M.,
Trevisan, C. P.,
El Messlemani, A. H.,
Tarone, G.,
Engvall, E.,
Hoffman, E. P.,
and Angelini, C.
(2002)
Am. J. Pathol.
160,
2135-2143 |
52. | Velling, T., Collo, G., Sorokin, L., Durbeej, M., Zhang, H., and Gullberg, D. (1996) Dev. Dyn. 207, 355-371[CrossRef][Medline] [Order article via Infotrieve] |
53. | Hayashi, Y. K., Chou, F. L., Engvall, E., Ogawa, M., Matsuda, C., Hirabayashi, S., Yokochi, K., Ziober, B. L., Kramer, R. H., Kaufman, S. J., Ozawa, E., Goto, Y., Nonaka, I., Tsukahara, T., Wang, J. Z., Hoffman, E. P., and Arahata, K. (1998) Nat. Genet. 19, 94-97[Medline] [Order article via Infotrieve] |
54. | Cohn, R. D., Mayer, U., Saher, G., Herrmann, R., van der Flier, A., Sonnenberg, A., Sorokin, L., and Voit, T. (1999) J. Neurol. Sci. 163, 140-152[CrossRef][Medline] [Order article via Infotrieve] |
55. | Song, W. K., Wang, W., Foster, R. F., Bielser, D. A., and Kaufman, S. J. (1992) J. Cell Biol. 117, 643-657[Abstract] |
56. |
Yao, C. C.,
Breuss, J.,
Pytela, R.,
and Kramer, R. H.
(1997)
J. Cell Sci.
110,
1477-1487 |
57. |
Werner, A.,
Willem, M.,
Jones, L. L.,
Kreutzberg, G. W.,
Mayer, U.,
and Raivich, G.
(2000)
J. Neurosci.
20,
1822-1830 |
58. | Klaffky, E., Williams, R., Yao, C. C., Ziober, B., Kramer, R., and Sutherland, A. (2001) Dev. Biol. 239, 161-175[CrossRef][Medline] [Order article via Infotrieve] |
59. | Schöber, S., Mielenz, D., Echtermeyer, F., Hapke, S., Pöschl, E., von der Mark, H., Moch, H., and von der Mark, K. (2000) Exp. Cell Res. 255, 303-313[CrossRef][Medline] [Order article via Infotrieve] |
60. | Ziober, B. L., Chen, Y., and Kramer, R. H. (1997) Mol. Biol. Cell 8, 1723-1734[Abstract] |
61. | Sorokin, L. M., Maley, M. A., Moch, H., von der Mark, H., von der Mark, K., Cadalbert, L., Karosi, S., Davies, M. J., McGeachie, J. K., and Grounds, M. D. (2000) Exp. Cell Res. 256, 500-514[CrossRef][Medline] [Order article via Infotrieve] |
62. |
Belkin, A. M.,
Retta, S. F.,
Pletjushkina, O. Y.,
Balzac, F.,
Silengo, L.,
Fässler, R.,
Koteliansky, V. E.,
Burridge, K.,
and Tarone, G.
(1997)
J. Cell Biol.
139,
1583-1595 |
63. |
Belkin, A. M.,
and Retta, S. F.
(1998)
J. Biol. Chem.
273,
15234-15240 |
64. |
Baudoin, C.,
Goumans, M. J.,
Mummery, C.,
and Sonnenberg, A.
(1998)
Genes Dev.
12,
1202-1216 |
65. | Rando, T. A. (2001) Muscle Nerve 24, 1575-1594[CrossRef][Medline] [Order article via Infotrieve] |
66. | Burton, E. A., and Davies, K. E. (2002) Cell 108, 5-8[Medline] [Order article via Infotrieve] |
67. | Campbell, K. P. (1995) Cell 80, 675-679[Medline] [Order article via Infotrieve] |
68. | Xu, H., Wu, X. R., Wewer, U. M., and Engvall, E. (1994) Nat. Genet. 8, 297-302[Medline] [Order article via Infotrieve] |
69. | Helbling-Leclerc, A., Zhang, X., Topaloglu, H., Cruaud, C., Tesson, F., Weissenbach, J., Tome, F. M., Schwartz, K., Fardeau, M., Tryggvason, K., and Guicheney, P. (1995) Nat. Genet. 11, 216-218[Medline] [Order article via Infotrieve] |
70. | Miosge, N., Klenczar, C., Herken, R., Willem, M., and Mayer, U. (1999) Lab. Invest. 79, 1591-1599[Medline] [Order article via Infotrieve] |
71. | Brabant, M. C., and Brower, D. L. (1993) Dev. Biol. 157, 49-59[CrossRef][Medline] [Order article via Infotrieve] |
72. | Volk, T., Fessler, L. I., and Fessler, J. H. (1990) Cell 63, 525-536[Medline] [Order article via Infotrieve] |
73. |
Yang, J. T.,
Rayburn, H.,
and Hynes, R. O.
(1993)
Development
119,
1093-1105 |
74. |
Hodges, B. L.,
Hayashi, Y. K.,
Nonaka, I.,
Wang, W.,
Arahata, K.,
and Kaufman, S. J.
(1997)
J. Cell Sci.
110,
2873-2881 |
75. |
Vachon, P. H.,
Xu, H.,
Liu, L.,
Loechel, F.,
Hayashi, Y.,
Arahata, K.,
Reed, J. C.,
Wewer, U. M.,
and Engvall, E.
(1997)
J. Clin. Invest.
100,
1870-1881 |
76. |
Straub, V.,
Rafael, J. A.,
Chamberlain, J. S.,
and Campbell, K. P.
(1997)
J. Cell Biol.
139,
375-385 |
77. |
Allamand, V.,
and Campbell, K. P.
(2000)
Hum. Mol. Genet.
9,
2459-2467 |
78. |
Burkin, D. J.,
Wallace, G. Q.,
Nicol, K. J.,
Kaufman, D. J.,
and Kaufman, S. J.
(2001)
J. Cell Biol.
152,
1207-1218 |