Dissertation/Thesis Abstract

Neurolastin is a novel dynamin family large GTPase that regulates dendritic spines
by McNeil, Stephaine A. N., Ph.D., The Johns Hopkins University, 2012, 150; 3532390
Abstract (Summary)

In the mammalian brain, conventional excitatory communication between neurons is achieved through axonal contacts with spines, membranous structures protruding from dendrites. Spines are highly dynamic; rapid enlargement of spines, and increases in spine density, can enhance neuronal circuits. Large GTPases play critical roles in neurons to sustain synaptic architecture and function. Indeed, dynamins are principal mediators of endocytosis at synaptic sites while several other dynamin-like proteins (DLPs) regulate membrane dynamics of organelles, which are particularly important in elongated axons of neurons. Each of the seven currently known types of DLPs can target to, and regulate the dynamics of, specific cellular membranes. Here I have identified neurolastin as a novel, brain specific large GTPase localized to endosomes. I show that neurolastin is a functional GTPase with sequence homology to DLPs, and that it is capable of hydrolyzing GTP to GMP, similar to the guanylate-binding proteins (GBPs). Disruption of neurolastin's catalytic activity results in decreased dendritic spine density. Furthermore, neurolastin knockout mice have reduced dendritic spine density and, remarkably, this defect can be completely rescued by exogenous expression of wild type neurolastin. These results demonstrate that the GTPase activity of neurolastin is critical for maintaining neuronal structure. Here I introduce a neuron-specific DLP involved in dendritic spine density, and with the discovery of a new DLP, I provide new insight into this critically important family of proteins.

Indexing (document details)
Advisor: Roche, Katherine W.
Commitee:
School: The Johns Hopkins University
School Location: United States -- Maryland
Source: DAI-B 74/03(E), Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Molecular biology, Neurosciences, Cellular biology
Keywords: Dendritic spines, Large GTPases, Neurolastin, Ubiquitin
Publication Number: 3532390
ISBN: 9781267752253
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