Actin Isoforms in neuronal structure and function

Abstract

The actin cytoskeleton plays critical roles in nearly every aspect of neuronal development and function. During these processes, the localized polymerization of actin is one mechanism employed to carryout crucial tasks for normal neuronal function. While the activity of actin binding proteins is generally thought to be the primary mediator of spatially restricted actin polymerization, another prominent mechanism involves the local translation of β-actin, one of two actin isoforms expressed in neurons. The localized translation of β-actin has been shown previously to be essential for growth cone guidance in cultured neurons. Additionally, defects in the localization of β-actin have been implicated in the motor neuron disease Spinal Muscular Atrophy (SMA). However, no study to date has directly examined the role of β-actin in a mammalian in vivo system. Although the functions of β-actin were thought to be critical for all neurons, the work described in this thesis indicates that specific functions of β-actin are surprisingly confined to select populations in the central nervous system (CNS). β-actin is not required for motor axon regeneration or motor neuron function, but is required for the proper structure of the hippocampus, cerebellum, and corpus callosum, as well as hippocampal-associated behaviors. Thus, the work described here provides the first direct demonstration of specific roles for β-actin in vivo and presents a model to translate provocative findings in cell culture to the mammalian CNS.