Yoko Bekku, PhD

My major research interest is how non-neuronal cells, in particular myelinating Schwann cells and oligodendrocytes in the peripheral and central nervous systems, respectively, modulate axon form and function. Myelin formation supports axon integrity and is essential for action potential propagation via saltatory conduction. The importance of myelin, and myelinating glia, is underscored by the severe neurologic disability that results from loss of myelin (demyelination) in diseases such as Multiple Sclerosis. Loss of myelin is also increasingly appreciated to contribute to neurological deficits of aging.

Myelinating glia reorganize axons into polarized domains, notably the node of Ranvier – an electrogenic domain that is the site of action potential regeneration and propagation. The node of Ranvier, which comprises only about 1% of the length of the axon, exhibits a striking accumulation of ion channels, cell adhesion molecules (CAMs), and cytoskeletal proteins. Before myelination, these proteins are uniformly distributed along the entire length of the axon. With myelination, these proteins, including CAMs, are cleared from extranodal regions underneath the myelin sheath and accumulate at the node. These mechanisms: selective clearance and accumulation drive domain formation and are required for normal neuronal function.

My studies in the Salzer lab at the NYU Grossman School of Medicine focus on: 1) how axonal domain proteins are targeted to specific domains during myelination by transport and redistribution, 2) the role of clathrin-mediated endocytosis in driving clearance from extranodal sites during myelination, and 3) the role of these molecules in demyelination and neurodegeneration. In many demyelinating diseases, including multiple sclerosis, associated axon loss is a major source of clinical disability. I have developed a transgenic mouse line that exhibits late onset demyelination with axon loss that provides a novel model to study mechanisms of axonal degeneration.