All ETDs from UAB

Advisory Committee Chair

Gavin Rumbaugh

Advisory Committee Members

Scott Wilson

David Sweatt

Lori L McMahon

Harald Sontheimer

Document Type

Dissertation

Date of Award

2011

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Cytoskeletal actin filaments underlie dendritic spine plasticity, critical for several forms of learning and memory. Therefore, understanding the mechanisms that regulate actin dynamics is essential to elucidate memory formation pathways. Myosins, a superfamily of actin binding proteins, have emerged as candidates for regulation of actin dynamics in the brain. Several myosin class II isoforms have been identified in brain, but their individual contribution to synaptic activity is still unknown. Based on the finding that myosin IIB regulates actin polymerization in the growth cone of developing neurons and that it is necessary for maintenance of dendritic spine structure, I hypothesized that in dendritic spines myosin IIB regulates actin dynamics, affecting synaptic transmission. I show that in addition to basal transmission, myosin IIB affects the maintenance of long term potentiation through a mechanism leading to reorganization and de novo synthesis of actin filaments. I further show that myosin IIB activity on actin filaments is critical for long-term memory consolidation. In addition to advancing our understanding of myosin IIB function in neurons, I was also able to characterize and identify a distinct muscle isoform of myosin II, MyH7B, in brain. The effects on dendritic spine morphology and synaptic strength of this isoform are different from those of myosin IIB. MyH7B acts as a structural myosin that maintains synaptic morphology and regulates trafficking of AMPA receptors to the synaptic surface through its activity on actin filament dynamics. Through my research I was able to identify a novel function for two distinct myosin II isoforms in brain, finding them critical for synaptic activity.

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