TY - JOUR
T1 - Dependence of myoblast fusion on a cortical actin wall and nonmuscle myosin IIA
AU - Duan, Rui
AU - Gallagher, Patricia J.
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health (NHLBI HL54118 and DK062810) to P. J. G. We thank Dr. Vincent H. Gattone and Janice Pennington for EM technical support and Dr. Susan Gunst for assistance with the F/G actin assay and MetaMorph™ software. We also thank Dr. Fred Pavalko for immuno-fluorescence microscopy support, Dr. Jiliang Zhou and Min Zhang for qRT-PCR support and members of the Gallagher, Herring and Elmendorf lab as well as Dr. Elizabeth Chen (JHU) for useful discussions.
PY - 2009/1/15
Y1 - 2009/1/15
N2 - Cell-cell fusion is a fundamental cellular process that is essential for development as well as fertilization. Myoblast fusion to form multinucleated skeletal muscle myotubes is a well studied, yet incompletely understood example of cell-cell fusion that is essential for formation of contractile skeletal muscle tissue. Studies in this report identify several novel cytoskeletal events essential to an early phase of myoblast fusion among cultured murine myoblasts. During myoblast pairing and alignment, cortical actin filaments organize into a dense actin wall structure that parallels and extends the length of the plasma membrane of the bipolar, aligned cells. As fusion progresses, gaps appear within the actin wall at sites of vesicle accumulation, the vesicles pair across the aligned myoblasts, cell-cell contacts and fusion pores form. Inhibition of nonmuscle myosin IIA (NM-MHC-IIA) motor activity prevents formation of this cortical actin wall, as well as the appearance of vesicles at a membrane proximal location, and myoblast fusion. These results suggest that early formation of a subplasmalemmal actin wall during myoblast alignment is a critical event for myoblast fusion that supports bipolar membrane alignment and temporally regulates trafficking of vesicles to the nascent fusion sites during skeletal muscle myoblast differentiation.
AB - Cell-cell fusion is a fundamental cellular process that is essential for development as well as fertilization. Myoblast fusion to form multinucleated skeletal muscle myotubes is a well studied, yet incompletely understood example of cell-cell fusion that is essential for formation of contractile skeletal muscle tissue. Studies in this report identify several novel cytoskeletal events essential to an early phase of myoblast fusion among cultured murine myoblasts. During myoblast pairing and alignment, cortical actin filaments organize into a dense actin wall structure that parallels and extends the length of the plasma membrane of the bipolar, aligned cells. As fusion progresses, gaps appear within the actin wall at sites of vesicle accumulation, the vesicles pair across the aligned myoblasts, cell-cell contacts and fusion pores form. Inhibition of nonmuscle myosin IIA (NM-MHC-IIA) motor activity prevents formation of this cortical actin wall, as well as the appearance of vesicles at a membrane proximal location, and myoblast fusion. These results suggest that early formation of a subplasmalemmal actin wall during myoblast alignment is a critical event for myoblast fusion that supports bipolar membrane alignment and temporally regulates trafficking of vesicles to the nascent fusion sites during skeletal muscle myoblast differentiation.
KW - Actin
KW - Myoblast fusion
KW - Nonmuscle myosin II
KW - Skeletal muscle development
KW - Vesicle pairing
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U2 - 10.1016/j.ydbio.2008.10.035
DO - 10.1016/j.ydbio.2008.10.035
M3 - Article
C2 - 19027000
AN - SCOPUS:58149116454
SN - 0012-1606
VL - 325
SP - 374
EP - 385
JO - Developmental biology
JF - Developmental biology
IS - 2
ER -