Abstract/Details

Myosin II in hippocampal synapses: Regulation of synaptic plasticity, strength and actin dynamics by two distinct isoforms


2011 2011

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Abstract (summary)

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.

Keywords: actin, myosin, dendritic spine, synaptic transmission, AMPA receptors, plasticity.

Indexing (details)


Subject
Molecular biology;
Neurosciences
Classification
0307: Molecular biology
0317: Neurosciences
Identifier / keyword
Biological sciences; Actin; Dendritic spines; Learning; Long-term potentiation; Memory; Myosin; Synaptic plasticity
Title
Myosin II in hippocampal synapses: Regulation of synaptic plasticity, strength and actin dynamics by two distinct isoforms
Author
Rubio, Maria Dolores
Number of pages
213
Publication year
2011
Degree date
2011
School code
0005
Source
DAI-B 72/08, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9781124672885
Advisor
Rumbaugh, Gavin
Committee member
McMahon, Lori; Sontheimer, Harald; Sweatt, David; Wilson, Scott
University/institution
The University of Alabama at Birmingham
Department
Neurobiology
University location
United States -- Alabama
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3457194
ProQuest document ID
873456217
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/873456217
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