A joint project of the Graduate School, Peabody College, and the Jean & Alexander Heard Library

Title page for ETD etd-06052011-205119


Type of Document Dissertation
Author Lin, Wan-Hsin
URN etd-06052011-205119
Title Vasodilator-stimulated phosphoprotein(VASP) promotes actin assembly in dendritic spines to regulate synaptic strength
Degree PhD
Department Biological Sciences
Advisory Committee
Advisor Name Title
Charles Singleton Committee Chair
Keywords
  • AMPA receptor
  • synaptic strength
  • spine morphogenesis
  • actin
  • VASP
  • synapse formation
Date of Defense 2011-05-03
Availability unrestricted
Abstract
Dendritic spines are small actin-rich structures that receive the majority of excitatory synaptic input in the brain. The actin-based dynamics of spines are thought to mediate synaptic plasticity, which underlies cognitive processes such as learning and memory. However, little is known about the molecular mechanisms that regulate actin dynamics in spines and synapses. In this study, we show that the multifunctional actin-binding protein VASP regulates the density, size, and morphology of dendritic spines by inducing actin assembly in these structures. Knockdown of endogenous VASP by siRNA led to a significant decrease in the density of spines and synapses, while expression of siRNA-resistant VASP rescued this defect. The ability of VASP to modulate spine and synapse formation, maturation, and spine head enlargement is dependent on its actin-binding Ena/VASP homology 2 (EVH2) domain and its EVH1 domain, which contributes to VASP localization to actin-rich structures. Moreover, VASP increases the amount of PSD scaffolding proteins and the number of surface GluR1-containing a-amino-3-hydroxy-5-methyl-4-

isoxazole propionic acid (AMPA) receptors in spines. VASP knockdown results in a reduction in surface AMPA receptor density, suggesting a role for this protein in regulating synaptic strength. Consistent with this, VASP significantly enhances the retention of GluR1 in spines as determined by fluorescence recovery after photobleaching (FRAP) and increases AMPA receptors-mediated synaptic transmission. Collectively, our results suggest that actin polymerization and bundling by VASP are critical for spine formation, spine expansion, and the modulation of synaptic strength.

Files
  Filename       Size       Approximate Download Time (Hours:Minutes:Seconds) 
 
 28.8 Modem   56K Modem   ISDN (64 Kb)   ISDN (128 Kb)   Higher-speed Access 
  Dissertation.pdf 10.05 Mb 00:46:30 00:23:55 00:20:55 00:10:27 00:00:53

Browse All Available ETDs by ( Author | Department )

If you have more questions or technical problems, please Contact LITS.