Yelena Leitman

The goal of our research is to elucidate the molecular mechanisms responsible for the formation of the myelin sheath, a structure that facilitates the efficient and rapid propagation of action potentials by saltatory conduction. During myelin formation, specialized glial cells: Schwann cells (SC) in the peripheral nervous system (PNS) and oligodendrocytes (OL) in the central nervous system (CNS), undergo a dramatic reorganization of their cytoskeleton, extending plasma membrane processes that wrap around axons. Two important participants in such events are actin and the actin-associated motor protein myosin II. Activity of myosin II is regulated via phosphorylation of myosin light chain (MLC) which promotes stability and contractability of actomyosin. Several kinases can phosphorylate MLC, including Rho-associated kinase (ROCK) and myosin light chain kinase (MLCK). Our data suggest that these kinases might regulate distinct aspects of myelin formation, specifically regulation of myelin morphology by ROCK and spiral wrapping by MLCK. We speculate that such effects may be an outcome of differential localization of ROCK and MLCK in glial cells and thus their association with distinct pools of actomyosin during myelination. Understanding of the molecular basis of myelination in both the PNS and CNS should help in the development of therapeutic strategies aimed to promote re-myelination and treat human diseases such as Multiple Sclerosis where myelin is lost.