Laboratoire de morphogénèse et signalisation cellulaires, Institut Curie UMR 144, 75248 Paris cedex 05, France
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Villin plays a key role in the maintenance of the brush border organization by bundling F-actin into a network of parallel filaments. Our previous in vivo data on villin knockout mice showed that, although this protein is not necessary for the bundling of F-actin, it is important for the reorganization of the actin cytoskeleton elicited by stress conditions. We further investigated villin property to initiate actin remodeling in cellular processes such as hepatocyte growth factor-induced motility, morphogenesis, and bacterial infection. Our data suggest that villin is involved in actin remodeling necessary for many cellular processes requiring the actin cytoskeleton plasticity.
F-actin; gelsolin family; cell motility; Shigella infection
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
SIMPLE EPITHELIA ARE ORGANIZED into sheets of contiguous cells that cover surfaces of organs to separate external from internal compartments. Differentiated epithelial cells are characterized by an apical-basolateral polarity and specialized cell-cell contacts. Junctional complexes, such as adherens and tight junctions, promote cell-cell adhesion. Epithelial cells exhibit a structural asymmetry of the cytoplasm, and the plasma membrane is compartimentalized into distinct apical and basolateral domains with characteristic lipid and protein compositions. Depolarization, loss of adhesiveness, and invasion of epithelial cells occur in normal processes and, in a deregulated manner, during carcinogenesis. Loss of polarity is part of the adaptative process that allows cells to respond efficiently to environmental signals, notably by migration events (i.e., organ development and remodeling and woundhealing). Cancer cells, by definition, proliferate and invade tissues in defiance of normal control. These cells lose an important characteristic of epithelia, which is contact inhibition, that helps to maintain an organized epithelial structure.
A unique feature of intestinal epithelial cells is the presence of a brush border composed of numerous membrane extensions called microvilli, fingerlike extensions that play a key role in the absorptive function of these specialized cells. They are abundant on those epithelial cells that require a very large surface area to function efficiently. Each microvillus is ~0.08 µm wide and 1 µm long, making the cell's absorptive area 20 times greater than it would be without them. The plasma membrane that covers these microvilli is highly specialized, bearing a thick extracellular coat of polysaccharide and digestive enzymes. The core of each intestinal microvillus is a rigid bundle of 20-30 parallel actin filaments that extend from the tip of the microvillus down into the cell cortex. The actin filaments in the bundle are all oriented with their plus ends pointing away from the cell body. They are held together at regular intervals by actin-bundling proteins. Fimbrin, an ubiquitous actin-binding protein, is involved in actin microfilament organization in microspikes and filipodia, and it also contributes to the bundling of actin filaments into microvilli. By contrast, villin is only found in microvilli of the digestive and urinary tracts, where it is known to bundle actin filaments, thus playing a key role in the maintenance of brush border architecture.
![]() |
VILLIN, A STRUCTURAL ACTIN-BINDING PROTEIN |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Structure
Villin is a tissue-specific actin-binding protein expressed in the brush border of enterocytes and proximal kidney cells. The gelsolin family, to which villin belongs, contains several members: gelsolin, adseverin, CapG, advillin, and supervillin. These proteins all contain three to six homologous evolutionarily conserved domains (Fig. 1). The typical villins have six of these, and, in addition, they have a so-called "headpiece" at the COOH terminus, which is the largest single difference between gelsolin and villins (for review see Ref. 6). In vertebrates, villin expression tends to be limited to the brush border. Surprisingly, villins or villin-like proteins, also expressed in protists and plants (11), do not seem to be associated with microvilli-like structures.
|
The solution structure of the NH2-terminal domain of villin
(14T, amino acids 1-126) has been determined by heteronuclear resonance spectroscopy. A central -sheet with four antiparallel strands and a fifth parallel strand on one edge forms the core structure that is surrounded by amphipathic helixes, two on one side
and a two-stranded parallel
-sheet with another helix on the other
side. Mutational analyses of villin suggest that the actin-binding
region is localized near the parallel strand at the edge of the central
-sheet. Recently, the nuclear magnetic resonance structure of the 35 COOH-terminal residues of chicken villin was established
(25). This sequence forms an autonomously folding
subdomain that comprises three helixes. The hydrophobic side chains of
the three helixes contribute to a compact hydrophobic core structure.
Function
Villin (17), gelsolin (12), adseverin (13), and CapG (15) have the common property of binding to barbed ends of actin filaments with high affinity. Villin, gelsolin, and adseverin can sever actin filaments, whereas CapG lacks this activity (26). Among all actin-binding proteins, villin is unique in presenting capping, bundling, and severing properties in a single protein.Villin, first isolated from chicken intestinal epithelial cells and later from mammalian species, is an acidic polypeptide with a molecular mass of 92.5 kDa, occuring in monomeric form. Villin can be phosphorylated on tyrosine residues in response to carbachol treatment of ileal mucosa (10).
Villin contains at least three actin-binding sites, two of which are Ca2+ dependent and located on the core domain (Kd = 7 µM). The third one, Ca2+ independent, is situated on the headpiece domain (Kd = 0.3 µM). Villin sequences involved in F-actin binding have been mapped using synthetic peptides. A cluster of charged amino acids located at the interdomain region of domains 1-2 (amino acids 133-147) is part of the F-actin binding site of the core domain. Binding of phosphatidylinositol 4,5-biphosphate (PIP2) to this sequence inhibits its interaction with actin. The actin binding site of the headpiece domain is located at the COOH terminus of villin and also comprises a charged motif of amino acids, KKEK (amino acids 820-823), which is conserved throughout species. More recently, proteins containing a domain with similarities to the headpiece and that are likely to provide actin-binding activity have been identified. This includes the two subunits of dematin (23), abLIM (24), and supervillin (p205) (19). Moreover, among the gelsolin/villin family members, advillin (p92) is the only one presenting a KKEK motif (14) and a conserved lysine at position 815 in the headpiece domain. These sites have been shown to be critical for actin binding (3). These authors propose that the presence of advillin in intestinal brush border could explain the absence of phenotype in villin knockout (KO) mice, thus allowing to compensate villin actin-bundling property.
Two rapidly exchanging Ca2+-binding sites have been
determined, one located in the core domain
(Kd = 3.5 × 106 M) and
one in the headpiece (Kd = 7.4 × 10
6 M). A third, nonexchangeable high-affinity site is
located in the core domain. Binding of Ca2+ to that located
in the headpiece induces a conformational change of the core part of
the molecule and thereby may induce a change in the molecule's
biochemical behavior.
Villin is a marker for a few cell types in adults and in embryos and a differentiation marker for epithelial cells displaying a brush border (for review see Ref. 6). With the use of immunocytochemical techniques, villin has been detected only in a few epithelial cells from the gastrointestinal, the urogenital, and the respiratory tracts. In adults, villin synthesis increases during the differentiation process of the enterocyte, which takes place when the enterocytes migrate along from crypt to the tip of the intestinal villus. During early embryonic development in chicken and mouse, villin is detectable in cells of the primitive gut, which are precursors of the adult intestine. A 9-kb regulatory region of the mouse villin gene contains the necessary cis-acting elements to recapitulate the tissue-specific expression pattern of the endogenous villin gene that can be used to drive the expression of heterologous genes in immature and differentiated epithelial cells of the small and/or large intestinal mucosa (21).
Several lines of evidence suggest that villin participates in the assembly of the intestinal brush border cytoskeleton (for review see Ref. 6). 1) In vitro reconstitution experiments show that villin and fimbrin, another major actin-binding protein of the brush border, dictate the structural organization of the microvillar core actin filament bundle. Addition of these two proteins to pure G-actin results in the formation of actin bundles consisting of oriented actin filaments that exhibit almost the same periodical arrangement as those of the brush border. 2) In a different approach, the effect of villin on organization of actin microfilaments was investigated by transfection of human villin cDNA in cell lines that do not produce villin and do not form a brush border. In these cells, large amounts of villin induce the growth of microvilli and a reorganization of actin microfilaments. The conserved KKEK motif, sequence part of an actin-binding site at the COOH terminal of villin, is essential for its morphogenic activity in cell cultures (7). In addition, Caco-2 cells, in which villin synthesis is impaired by transfection of a construct producing antisense mRNA for villin, do not form a brush border (2).
![]() |
VILLIN, AN ACTIN REMODELING PROTEIN |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Villin KO Mice
Ferrary et al. (5) and Pinson et al. (20) have shown that the ultrastructural organization of microvilli is not altered in vil ![]() |
HOW CAN VILLIN BE INVOLVED IN THE ACTIN CYTOSKELETON DYNAMICS? |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Epithelial cell dispersal during cell motility is a complex
process that requires the breakdown of cell-cell junctions in addition
to the remodeling of both the actin cytoskeleton and cell-adhesion
complexes. These changes contribute to a transition from an epithelial
morphology toward a more mesenchymal fibroblastic phenotype, referred
to as epithelial-mesenchyme transition, modulated by hepatocyte growth
factor (HGF) and its receptor, the tyrosine kinase
c-met. Several intracellular signaling pathways have been shown to act downstream of the HGF receptor to mediate scattering or
tubulogenesis response. For example, c-met was reported to directly interact with signaling proteins, including phospholipase C
(PLC) (22). Furthermore, it has been reported that
villin interacts with several signaling molecules including PLC
(18), PIP2 (8), and calcium
(9). In vitro, villin tyrosine phosphorylation has been
shown to enhance actin severing and to inhibit villin actin bundling
property (27). These findings suggest that villin could
play an essential role in the actin cytoskeleton dynamics in response
to specific physiological stimuli. We have developed several approaches
to evaluate the role of villin in cellular events that require actin
cytoskeleton plasticity and remodeling, such as cell motility, cell
morphogenesis, and bacterial infections. These studies were performed
using primary cultures of enterocytes derived from vil+/+
and vil
/
mice and Tet Off Madin-Darby canine kidney
(MDCK) cells expressing the villin transgene in a
doxycycline-controlled manner. We show that villin plays a role as a
potentiator of the actin cytoskeleton dynamics elicited by
extracellular signals. Indeed, we have found that villin is an enhancer
of HGF-induced cell motility and morphogenesis. Moreover, its role as a
potentiator of actin dynamics on growth factor stimulation takes place
through the PLC
-signaling pathway (R. Athman, unpublished data).
The actin cytoskeleton remodeling is also required in other cellular
processes such as bacterial infection. Shigella flexneri is
the causative agent of bacillary dysentery. This gram-negative pathogen
induces the reorganization of the host actin cytoskeleton during the
infectious process. The main target of this bacterium being the
enterocyte, we took advantage of our villin KO model to study the
infectious process in intestinal primary cultures from
vil+/+ and vil/
mice. This work is in
progress in collaboration with D. Philpott and P. Sansonetti (Institut
Pasteur). We have shown, using primary cultures of enterocytes, that
villin is involved in bacterial entry and cell-cell dissemination.
Villin is present in the actin comet formed by intracellular bacteria.
Together, these results indicate that villin plays an important role in
the different steps of Shigella infection through its
ability to remodel the actin cytoskeleton reorganization elicited by
the invasion process (R. Athman, unpublished data).
![]() |
VILLIN AS A REGULATOR OF ACTIN DYNAMICS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Background on Actin Dynamics
Gel/sol state of actin. In vitro, filamentous actin (F-actin) tends to be liquidlike and its viscosity low (sol state), without cross-linking proteins. The addition of cross-linking proteins, also called actin binding proteins, leads to the formation of dense F-actin meshworks and changes the mechanical properties (viscoelasticity) of the solution. This state is characterized by a high viscosity and higher resistance to physical deformation and is called the gel state. The critical concentration of cross-linking protein needed to induce a significant increase in viscosity is proportional to the polymer concentration over the polymer length. Shortening of cross-linked actin filaments by severing reverts the gel state to the sol state, as does reversal of cross-linking.
In cells, effective actin-based motility is not possible without cross-linking and bundling. The dynamics of actin networks include actin filament assembly, cross-linking, bundling, actin filament disassembly, actin monomer sequestration, and recycling. Dynamic actin-based structures are important in eukaryotic cell shape change and motility, cytokinesis, endocytosis, and other processes both normal and pathological.Actors of actin dynamics. Proteins of the gelsolin family are regulated by calcium (which activates severing and/or capping) and certain inositol phospholipids (which cause uncapping, the release of actin filament barbed ends, and thus allow for actin polymerization from the barbed ends). In the case of gelsolin itself, there is both a widely expressed intracellular form and a higher-molecular-weight extracellular form found in plasma; this latter form appears to play a role in scavenging extracellular actin released from lysed cells. CapZ is a calcium-independent heterodimeric protein that caps barbed ends of filaments in platelets, which appears to be coordinated with severing and capping by gelsolin family proteins. Actin-depolymerizing factor (ADF)/cofilin family proteins are calcium independent and also promote actin filament disassembly; however, the activity of these proteins differs from that of gelsolin family proteins. ADF/cofilin proteins appear to accelerate depolymerization from the pointed ends of actin filaments and to weakly sever filaments without capping. Arp2/3 complex and associated factors appear to promote actin filament assembly by de novo nucleation (or stabilization of nuclei), complementing assembly from barbed ends of existing filaments following barbed-end uncapping. This complex forms a cap on filament pointed ends and may also help to establish a branched actin filament geometry by binding to the sides of existing filaments.
Proteins that promote disassembly of actin filaments or cap filament barbed ends play roles in actin dynamics and cell motility. Actin assembly can be initiated by 1) de novo nucleation (or stabilization of nuclei) with the involvement of the Arp2/3 complex and 2) by Rac and phosphoinositide-regulated release of capping and/or severing proteins of the gelsolin/villin family (CapG, gelsolin, villin, and adseverin) and the CapZ family of capping proteins, from the barbed ends of actin filaments. Actin filament severing by gelsolin family or ADF/cofilin family proteins could also in itself be a mechanism of generating more free barbed ends from existing filaments. ![]() |
HOW CAN VILLIN ENHANCE ACTIN DYNAMICS DURING CELL MOTILITY? |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
There are a number of different types of actin-based motility, in contrast, different cells seem to move using different strategies. However, there are some general properties of cell movement. In general, the leading edge of a moving cell is the main site of actin assembly and cross-linking (or gelation, a type of "solidification" of the cytoplasm). The leading edge of an animal cell can display a variety of types of protrusion: lamellipodia, filopodia (also known as microspikes), and pseudopodia. In general, behind the protrusive structure, there is a region of active actin disassembly, where filaments are shortened and cross-links disrupted. Actin monomers resulting from this disassembly appear to then flow forward, where they can be added to the barbed ends of polymerizing filaments at the leading edge. Treadmilling allows continuous polymerization at barbed (plus) ends while disassembling continuously at pointed (minus) ends, without net increase in polymer mass. This type of polymerization can exert force and push out the plasma membrane during protrusion or power the movement of intracellular bacteria (e.g., Listeria).
ADF/cofilin proteins appear to weakly sever filaments without capping and could perhaps generate new free barbed ends to support polymerization. These proteins are most active not directly adjacent to the leading edge of motile cells but somewhat behind it, and such ends would be rapidly capped because there are high concentrations of capping proteins in the typical cell. The ends would have to be uncapped or prevented from being capped in the first place (by phosphoinositides) to support further elongation, which, again, would make uncapping a major control point for generation of free barbed ends from existing filaments. Certainly for villin that sever filaments, capping is an obligate part of the mechanism, which also means that subsequent uncapping is necessary for existing filaments to elongate. Actin disassembly generally occurs behind the leading edge and can be mediated by proteins of both the calcium-activated gelsolin family and the calcium-independent ADF/cofilin family (also known as actophorin, destrin, or depactin). The mechanism of action of these proteins is distinct but overlapping with that of severing proteins of the gelsolin/villin family. Phosphoinisotides appear to inhibit the function of gelsolin family, CapZ family, and ADF/cofilin family members, whereas calcium positively regulates the function of proteins of the gelsolin family. Phosphorylation but not calcium appears to regulate the activity of ADF/cofilin proteins (for general review, see Ref. 1).
Although the proteins involved in the actin dynamics are well identified, it is not so clear to determine how these proteins are involved in the integration of signals that initiate motility or maintain chemotaxis toward or away from a stimulus source. How cells coordinate movement in the organism or how cancer cells initiate metastasis are still open questions. Movement is a challenge that different cells solve, at least in part, and sometimes very differently.
In addition, different types of cells are fine tuned for a
specific structure or function by modifying the expression or
regulation of many proteins. For example, how do intestinal epithelial
cells forming well-organized microvilli maintained by actin bundles respond to extracellular signals or face cell damage? The apical actin-rich domain also contains actin-binding proteins necessary for
actin structural organization, as we discussed earlier. We propose that
the epithelium mesenchyme transition process requires both the
recruitment of apical actin and actin-binding proteins bearing
multifunctional properties, such as villin, enrichment of which at the
cell leading edge enables one to increase the dynamic process
necessary for cell propulsion. We suggest that the signaling
events leading to actin dynamics are mediated by proteins that are
specific to the epithelial lineage considered and are therefore
recruited to ensure dynamic functions, thus increasing the efficiency
of the cellular response. This adaptative process is necessary for
epithelial cells to make a rapid and efficient response to
extracellular signals during physiological or pathological situations
without any de novo protein synthesis. On the contrary, how can a
protein, in which expression is restricted to a defined tissue, be
integrated into signaling pathways and play an active role when
expressed in another cellular context? MDCK cells, routinely used for
cell motility and morphogenesis experiments, are able to easily perform
the epithelium-mesenchyme transition by using some actors of the
minimal molecular machinery described in the previous section. Addition
of villin to a cell that does not express this multifunctional protein
can lead to an increased turnover of actin monomers in the
polymerization/depolymerization cycle of actin that controls the
dynamics of cell motility, thus acting as a potentiator (Fig.
2).
|
Clinical Applications of Villin
As an intestinal marker. Because villin expression is maintained in neoplasic tissues, villin is a useful marker for primary tumors or metastases deriving from tissues that normally express villin (16). Its presence in the blood of patients presenting colorectal carcinomas makes it a diagnostic adjunct for the detection of these cancers (4).
As an actin-remodeling protein.
Our in vivo studies performed on vil+/+ and
vil/
mice by administration of dextran sodium sulfate,
an abrasive agent of the intestinal epithelium, have shown a higher
death probability of vil
/
mice, indicating their higher
susceptibility to cell damage. This allowed us to suggest a role for
villin in epithelial cell plasticity in response to cell injury. This
model of intestinal injury, close to other animal models of rectolitis,
can lead, in a long-term project, to a useful investigation of villin
status in human colonic diseases such as inflammatory bowel disease
(IBD). A genetic predisposition has been suggested, and many
environmental factors, including bacterial, viral, and, perhaps,
dietary antigens, can trigger an ongoing enteric inflammatory cascade
during IBDs. This raises the question of how epithelial cells interact
with components of the immune system and manage to promote the
epithelial mesenchyme transition in response to injury. The
investigation of villin expression levels or mutations in the context
of IBDs can contribute to the understanding of IBD pathogenesis.
![]() |
FOOTNOTES |
---|
Address for reprint requests and other correspondence: S. Robine, Laboratoire de morphogénèse et signalisation cellulaires, Institut Curie UMR 144, 26 rue d'Ulm, 75248 Paris cedex 05, France (E-mail: sylvie.robine{at}curie.fr).
10.1152/ajpgi.00207.2002
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Cooper, JA,
and
Schafer DA.
Control of actin assembly and disassembly at filament ends.
Curr Opin Cell Biol
12:
97-103,
2000[ISI][Medline].
2.
Costa de Beauregard, MA,
Pringault E,
Robine S,
and
Louvard D.
Suppression of villin expression by antisense RNA impairs brush border assembly in polarized epithelial intestinal cells.
EMBO J
14:
409-421,
1995[Abstract].
3.
Doering, DS,
and
Matsudaira P.
Cysteine scanning mutagenesis at 40 of 76 positions in villin headpiece maps the F-actin binding site and structural features of the domain.
Biochemistry
35:
12677-12685,
1996[ISI][Medline].
4.
Dudouet, B,
Robine S,
Huet C,
Sahuquillo-Merino C,
Blair L,
Coudrier E,
and
Louvard D.
Changes in villin synthesis and subcellular distribution during intestinal differentiation of HT29-18 clones.
J Cell Biol
105:
359-369,
1987[Abstract].
5.
Ferrary, E,
Cohen-Tannoudji M,
Pehau-Arnaudet G,
Lapillonne A,
Athman R,
Ruiz T,
Boulouha L,
El Marjou F,
Doye A,
Fontaine JJ,
Antony C,
Babinet C,
Louvard D,
Jaisser F,
and
Robine S.
In vivo, villin is required for Ca2+ dependent F-actin disruption in intestinal brush-borders.
J Cell Biol
146:
819-829,
1999
6.
Friederich, E,
Pringault E,
Arpin M,
and
Louvard D.
From the structure to the function of villin, an actin binding protein of the brush border.
Bioessays
12:
403-408,
1990[ISI][Medline].
7.
Friederich, E,
Vancompernolle K,
Huet C,
Goethals M,
Finidori J,
Vandekerckhove J,
and
Louvard D.
An actin binding site containing a conserved motif of charged amino acid residues is essential for the morphogenic effect of villin.
Cell
70:
81-92,
1992[ISI][Medline].
8.
Janmey, PA,
Iida K,
Yin HL,
and
Stossel TP.
Polyphosphoinositide micelles and polyphosphoinositide-containing vesicles dissociate endogenous gelsolin-actin complexes and promote actin assembly from the fast-growing end of actin filaments blocked by gelsolin.
J Biol Chem
262:
12228-12236,
1987
9.
Janmey, PA,
and
Matsudaira PT.
Functional comparison of villin and gelsolin. Effects of Ca2+, KCl, and polyphosphoinositides.
J Biol Chem
263:
16738-16743,
1988
10.
Khurana, S,
Arpin M,
Patterson R,
and
Donowitz M.
Ileal microvillar protein villin is tyrosine-phosphorylated and associates with PLC-1. Role of cytoskeletal rearrangement in the carbachol-induced inhibition of ileal NaCl absorption.
J Biol Chem
272:
30115-30121,
1997
11.
Klahre, U,
Friederich E,
Kost B,
Louvard D,
and
Chua NH.
Villin-like actin binding proteins are expressed ubiquitously in Arabidopsis.
Plant Physiol
122:
35-48,
2000
12.
Kwiatkowski, DJ,
and
Yin HL.
Molecular biology of gelsolin, a calcium-regulated actin filament severing protein.
Biorheology
24:
643-647,
1987[ISI][Medline].
13.
Lueck, A,
Brown D,
and
Kwiatkowski DJ.
The actin binding proteins adseverin and gelsolin are both highly expressed but differentially localized in kidney and intestine.
J Cell Sci
111:
3633-3643,
1998
14.
Marks, PW,
Arai M,
Bandura JL,
and
Kwiatkowski DJ.
Advillin (p92): a new member of the gelsolin/villin family of actin regulatory proteins.
J Cell Sci
111:
2129-2136,
1998
15.
Mishra, VS,
Henske EP,
Kwiatkowski DJ,
and
Southwick FS.
The human actin-regulatory protein cap G: gene structure and chromosome location.
Genomics
23:
560-565,
1994[ISI][Medline].
16.
Moll, R,
Robine S,
Dudouet B,
and
Louvard D.
Villin: a cytoskeletal protein and a differentiation marker expressed in some human adenocarcinomas.
Virchows Arch
54:
155-169,
1987.
17.
Northrop, J,
Weber A,
Mooseker MS,
Franzini-Armstrong C,
Bishop MF,
Dubyak GR,
Tucker M,
and
Walsh TP.
Different calcium dependence of the capping and cutting activities of villin.
J Biol Chem
261:
9274-9281,
1986
18.
Panebra, A,
Ma SX,
Zhai LW,
Wang XT,
Rhee SG,
and
Khurana S.
Regulation of phospholipase C-(1) by the actin-regulatory protein villin.
Am J Physiol Cell Physiol
281:
C1046-C1058,
2001
19.
Pestonjamasp, KN,
Pope RK,
Wulfkuhle JD,
and
Luna EJ.
Supervillin (p205): a novel membrane-associated, F-actin binding protein in the villin/gelsolin superfamily.
J Cell Biol
139:
1255-1269,
1997
20.
Pinson, KI,
Dunbar L,
Samuelson L,
and
Gumucio DL.
Targeted disruption of the mouse villin gene does not impair the morphogenesis of microvilli.
Dev Dyn
211:
109-121,
1998[ISI][Medline].
21.
Pinto, D,
Robine S,
Jaisser F,
El Marjou FE,
and
Louvard D.
Regulatory sequences of the mouse villin gene that efficiently drive transgenic expression in immature and differentiated epithelial cells of small and large intestines.
J Biol Chem
274:
6476-6482,
1999
22.
Ponzetto, C,
Bardelli A,
Zhen Z,
Maina F,
dalla Zonca P,
Giordano S,
Graziani A,
Panayotou G,
and
Comoglio PM.
A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family.
Cell
77:
261-271,
1994[ISI][Medline].
23.
Rana, AP,
Ruff P,
Maalouf GJ,
Speicher DW,
and
Chishti AH.
Cloning of human erythroid dematin reveals another member of the villin family.
Proc Natl Acad Sci USA
90:
6651-6655,
1993[Abstract].
24.
Roof, DJ,
Hayes A,
Adamian M,
Chishti AH,
and
Li T.
Molecular characterization of abLIM, a novel actin binding and double zinc finger protein.
J Cell Biol
138:
575-588,
1997
25.
Simenel, C,
Rose T,
Goethals M,
Vandekerckhove J,
Friederich E,
Louvard D,
and
Delepierre M.
Conformational behaviour of a synthetic peptide of the C-terminus of villin that interacts with actin: an NMR, CD and stimulated annealing study.
Int J Pept Protein Res
45:
574-586,
1995[ISI][Medline].
26.
Southwick, FS,
and
DiNubile MJ.
Rabbit alveolar macrophages contain a Ca2+-sensitive, 41,000-dalton protein which reversibly blocks the "barbed" ends of actin filaments but does not sever them.
J Biol Chem
261:
14191-14195,
1986
27.
Zhai, L,
Zhao P,
Panebra A,
Guerrerio AL,
and
Khurana S.
Tyrosine phosphorylation of villin regulates the organization of the actin cytoskeleton.
J Biol Chem
276:
36163-36167,
2001