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Shrager Lab
University of Rochester
work
Rochester
NY
Overview
Propagation of electrical signals with high speed and reliability in nerve fibers depends on a complex interaction between neurons and their associated myelinating glial cells. As a result of this interaction ion channels are clustered at specific sites along the axon. This system is studied in both development and disease. At birth axons have little myelin, but by the end of the first postnatal week both glial ensheathment and ion channel clustering are at an advanced state. In multiple sclerosis myelin is damaged, and ion channel distributions are disrupted. The immune mechanisms responsible for this pathology are not known. This laboratory studies the molecular mechanisms responsible for these phenomena using electrophysiology, immunocytochemistry, molecular biology, and transgenic manipulations.
During myelination glial cells have a profound influence on the axonal ion channel distribution. In the peripheral nervous system Schwann cells bind to axons during both development and remyelination. Sodium channels, responsible for the upstroke of the action potential, cluster in the axon membrane adjacent to the tips of Schwann cell processes that are extended during early stages of ensheathment. As Schwann cells grow longitudinally, these channels appear to move with them, ultimately fusing with a neighboring cluster to form a node of Ranvier. Voltage-dependent potassium channels have a reciprocal relationship with sodium channels, and are located primarily in clusters several micrometers on either side of the node. New studies are focused on the central nervous system and combine immunocytochemistry with electrophysiology to determine the distribution and role of ion channels during development of the optic nerve. We seek to determine the cellular and molecular events responsible for ion channel localization and stabilization in the neuronal membrane.
Recent Publications
- (2009 Mar 05). Early events in node of Ranvier formation during myelination and remyelination in the PNS. Neuron Glia Biol. 2, 69-79.
- (2008 Mar 13). Synaptic function for the Nogo-66 receptor NgR1: regulation of dendritic spine morphology and activity-dependent synaptic strength. J Neurosci. 28, 2753-65.
- (2007 Aug 28). Neurofascin assembles a specialized extracellular matrix at the axon initial segment. J Cell Biol. 178, 875-86.
