Title

Establishing and maintaining neuronal polarity: Form that fits function

Date of Completion

January 2007

Keywords

Biology, Neuroscience

Degree

Ph.D.

Abstract

The nervous system is a complex network of neurons and support cells. Neurons communicate with their target cells through electrical impulses and consequent chemical signaling. In order for neurons to communicate properly, the cells develop a complex morphology consisting of the somatodendritic and axon domains. The somatodendritic domain contains all the necessary components for receiving information from the preceding cells, while the axonal domain functions to relay information to the next cells of the network. While this subcellular polarization of neurons is necessary for function, neurons also depend on the establishment and maintenance of protein microdomains within the subcellular domains, or subdomain polarity. Cytoskeleton proteins and cell adhesion molecules contribute to neuronal function by (1) creating highly polarized domains across the entire neuron and (2) precisely localizing ion channels within the subcellular domains. Here, I focus on two molecularly and functionally similar domains, the axon initial segment (AIS) and node of Ranvier, to elucidate the mechanisms underlying neuronal polarity and ion channel clustering in axons. Neurons establish nodes of Ranvier through the extrinsic influence of myelinating glia and clustering of the cell adhesion molecule, neurofascin(NF)-186. However, a nearly functionally and molecularly identical microdomain, the axon initial segment (AIS), is established and maintained via intrinsic mechanisms through the cytoskeletal molecule, ankyrinG (ankG). Furthermore, axon specification and neuronal subcellular polarity depend on ankG localization and clustering at the AIS.^