American Journal of Physiology-Cell Physiology, Boston Biomedical Research Institute, 64 Grove St., Watertown, MA 02472, (E-mail: morgan{at}bbri.org), June 2001, Volume 280 (49)
THE FIELD OF "MUSCLE PHYSIOLOGY" has
traditionally included the study of mechanisms of contraction of
striated and smooth muscles under normal and pathophysiological
conditions. This special call for papers was initiated to
recognize the fact that the field has now evolved and expanded to
include complex considerations of the function and assembly of the
cytoskeleton as well as mechanisms of "nonmuscle motility."
Nonmuscle motility may at first seem a bit of an oxymoron, but the term
reflects the fact that actin and myosin regulate not just contraction
but also cell crawling, chemotaxis, cell shape, cytokinesis, and
phagocytosis, to name a few.
It has been known for some time that smooth muscle cells can crawl as
well as contract. Some investigators have suggested that extracellular
signal-regulated kinase/mitogen-activated protein kinases (ERK/MAPK)
and the actin binding protein caldesmon might regulate smooth muscle
contractility (1, 4, 5), although this remains highly
controversial (3, 9). Now, Yamboliev and Gerthoffer (Ref.
12, see p. C1680 in this issue) provide evidence that
ERK/MAPK, possibly through phosphorylation of caldesmon, can modulate
smooth muscle cell migration once it is initiated by appropriate
signaling pathways.
The division between muscle physiology and cell biology has become less
clear as the demonstration of the increasingly complex roles of actin
in muscle and nonmuscle cells has progressed. Clearly, actin and actin
binding proteins regulate myosin activity. However, actin, together
with the microtubules and intermediate filaments, also forms an
internal skeleton to physically support the cell. Where the story has
become especially complex (and interesting) is the realization that
signal transduction mechanisms are regulated by cytoskeletal components.
Rosado et al. (Ref. 10, see p. C1636 in this issue)
suggests that reorganization of the actin cytoskeleton, modulated by tumor necrosis factor- It has long been assumed that the actin cytoskeleton is a rather static
structure in differentiated muscle, but Conley (Ref. 2,
see p. C1645 in this issue), reporting on leiomodin and tropomodulin in
smooth muscle, makes the highly speculative but intriguing suggestion
that the smooth muscle cytoskeleton is in a state of dynamic flux
leading to actin filament remodeling during muscle contraction.
Although this remains a controversial topic, a body of evidence is
growing to support this concept (reviewed in Ref. 6), and
further investigation of actin capping proteins in differentiated
muscle may be warranted.
Cultured fibroblasts offer a model system for the study of cytoskeletal
function. Katoh et al. (Ref. 8, see p. C1669 in this
issue) provide evidence that there are two functionally different types
of stress fibers in these cells: central and peripheral stress fibers.
These authors suggest that the peripheral fibers are regulated, like
classic smooth muscle contractile filaments, by myosin light chain
kinase but that the central fibers are regulated primarily by Rho
kinase. These studies have implications not only for fibroblast cell
biology but also for smooth muscle physiologists who have suspected
that both kinases may play a role in the regulation of contraction
(11).
The determination of the precise role of cytoskeletal components in the
regulation of the physiology of muscle and nonmuscle cells poses
considerable challenges. Physiologists are often interested in
differentiated cells that are difficult to perturb with molecular precision. Furthermore, these perturbations often demonstrate tantalizing correlations, but true cause-and-effect relationships often
prove elusive. Despite these difficulties, the field is clearly growing
and merits the attention of physiologists not just in the muscle field
but also those studying nonmuscle cells, i.e., essentially all tissues
in the body.
ARTICLE
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ARTICLE
REFERENCES
, regulates store-mediated Ca2+
entry in a human hepatocellular carcinoma cell line. Similarly, Hamm-Alvarez et al. (Ref. 7, see p. C1657 in this issue)
present evidence that cytoplasmic non-receptor tyrosine kinases,
cytoskeletal components, and the regulation of cell-to-cell signaling
are interrelated.
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