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Myosin II has distinct functions in PNS and CNS myelin sheath formation

¹ Department of Biological Sciences, Hunter College, City University of New York, New York, NY 10065
² School of Health Sciences, Hunter College, City University of New York, New York, NY 10010
³ Department of Cell Biology and ⁴ Smilow Neuroscience Program, New York University School of Medicine, New York, NY 10016

Correspondence to Carmen V. Melendez-Vasquez: melendez{at}genectr.hunter.cuny.edu

The myelin sheath forms by the spiral wrapping of a glial membrane around the axon. The mechanisms responsible for this process are unknown but are likely to involve coordinated changes in the glial cell cytoskeleton. We have found that inhibition of myosin II, a key regulator of actin cytoskeleton dynamics, has remarkably opposite effects on myelin formation by Schwann cells (SC) and oligodendrocytes (OL). Myosin II is necessary for initial interactions between SC and axons, and its inhibition or down-regulation impairs their ability to segregate axons and elongate along them, preventing the formation of a 1:1 relationship, which is critical for peripheral nervous system myelination. In contrast, OL branching, differentiation, and myelin formation are potentiated by inhibition of myosin II. Thus, by controlling the spatial and localized activation of actin polymerization, myosin II regulates SC polarization and OL branching, and by extension their ability to form myelin. Our data indicate that the mechanisms regulating myelination in the peripheral and central nervous systems are distinct.

Abbreviations used in this paper: ANOVA, analysis of variance; bFGF, basic FGF; CNS, central nervous system; DRG, dorsal root ganglion; MBP, myelin basic protein; MLC, myosin light chain; N-WASP, neuronal Wiskott-Aldrich syndrome protein; OL, oligodendrocytes; OPC, OL precursor cells; PNS, peripheral nervous system; ROCK, Rho-associated kinase; SC, Schwann cells; shRNA, short hairpin RNA.

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