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

Abstract

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.

MLCK regulates Schwann cell cytoskeletal organization, differentiation and myelination

“…8F). Of note, pronounced ensheathment defects were also observed in SCs lacking MLC (Wang et al, 2008), thus confirming that myosin II activity is required for proper axonal segregation. Thus, despite undergoing differentiation, shMLCKtreated SCs are unable to properly segregate axons and therefore unable to myelinate.…”

“…Of interest, a similar correlation between downregulation of acto-myosin contractility and membrane extension has been recently described during morphological differentiation of oligodendrocytes (Kippert et al, 2009), suggesting that despite their different morphologies and modes of myelination, the mechanisms controlling plasma membrane expansion by myelinating glial cells require local release of myosin-II-mediated contraction and relaxation of the actin cytoskeleton. Whether MLCK activity also plays a role in oligodendrocyte remodeling and differentiation awaits further study, but inactivation of RhoA and ROCK as well as inhibition of myosin II have been shown to promote membrane expansion and oligodendrocyte branching and differentiation (Kippert et al, 2007;Wang et al, 2008;Wolf et al, 2001).…”

“…After 2-3 weeks in myelinating conditions, we examined the cultures for myelin basic protein (MBP) expression as previously described (Wang et al, 2008). We found that cultures established with MLCK-deficient SCs exhibited a significant reduction in the number of MBP + segments formed compared with controls ( Fig.…”

Withdrawal: Proteomic Profiling in the Spinal Cord and Sciatic Nerve in a Global Cerebral Ischemia-Induced Mechanical Allodynia Mouse Model

“…55,56) Myosin II is a hexameric complex composed of 2 myosin heavy chains, 2 MLCs, and 2 essential light chains. 57) Levels of non-muscle myosin II decrease as a function of oligodendrocyte differentiation and inhibition of myosin activity increases branching and myelination, 58,59) although their expression levels correlate negatively with myelination. 59,60) The demyelination observed in neuropathic pain due to nerve lysophosphatidic acid-induced injury occurs on Schwann cells.…”

“…57) Levels of non-muscle myosin II decrease as a function of oligodendrocyte differentiation and inhibition of myosin activity increases branching and myelination, 58,59) although their expression levels correlate negatively with myelination. 59,60) The demyelination observed in neuropathic pain due to nerve lysophosphatidic acid-induced injury occurs on Schwann cells. 61) By immunofluorescence staining, we observed that MLC2 was increased by global cerebral ischemia in the sciatic nerve.…”