Expression of Myosin II Isoforms in Myelinating Glial Cells

Alena Leitman, Department of Biological Sciences, Hunter College, City University of New York Haibo Wang, Department of Biological Sciences, Hunter College, City University of New York Ambika Tewari, Department of Biological Sciences, Hunter College, City University of New York Carmen V Melendez-Vasquez, Department of Biological Sciences, Hunter College, City University of New York

Abstract Myelin is a multilayered membranous sheath that allows the rapid propagation of electrical impulses by saltatory conduction. Myelin is formed by specialized glial cells: Schwann cells (SC) and oligodendrocytes (OL) that wrap around axons in the peripheral (PNS) and central (CNS) nervous systems respectively. The processes involved in myelin formation remain poorly understood but failure to myelinate or preserve the sheath intact cause severe neurological diseases. Recent data from our laboratory indicate that myosin II is a key regulator of glial cell cytoskeleton dynamics and myelination. Myosin II activity is necessary for SC differentiation. Thus, inhibition of myosin II prevents PNS myelination. By contrast in the CNS, inhibition of myosin II activity in OL promotes myelin formation. In order to understand the differential role of myosin II during myelin formation in the PNS and CNS, we have started to characterize the specific distribution of myosin II isoforms in SC and OL. We have found that all three isoforms of myosin II (A, B, and C) are expressed in SC and OL and appear to have differential localization and functions. In cultures of SC alone, myosin IIA and IIC staining is diffusely localized throughout the cell, whereas myosin IIB does not only predominate over IIA and IIC but is notably concentrated in stress fibers, at the leading edge, and at the retracting tail. In myelinating cocultures of SC and dorsal root ganglia (DRG) neurons, myosin IIB predominates at the initial stages of SC-axon contact, whereas the expression of IIC is increased in mature myelinating SC. In OL, myosin IIB is the prevailing isoform at the early stages of development. Staining for myosin IIB concentrates at the leading edge of growing OL processes but is downregulated during OL differentiation. Myosin IIC is not present in OL at the early stages, but its expression increases in differentiated cells. Taken together our data suggest that differential spatial and temporal expression of myosin II isoforms may play an important role in the mechanisms regulating myelin formation.

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