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Visualization of cadherin-cadherin association in living cells

Citation

Mosser, Eric A. (2007) Visualization of cadherin-cadherin association in living cells. Dissertation (Ph.D.), California Institute of Technology. http://resolver.caltech.edu/CaltechETD:etd-02142007-004140

Abstract

The almost universally accepted model for long-term potentiation (LTP) involves Ca2+ flux through NMDA receptors into dendritic spines. This Ca2+ influx may cause a transient Ca2+ decrease in the synaptic cleft. We hypothesize that this decrease in cleft Ca2+ may destabilize cadherin-cadherin bonds in the synapse and that this conformational change may allow synaptic cadherins to function as synaptic activity sensors.

In the last decade, much effort has been devoted to understanding the structure and molecular associations of classic cadherins. Crystallographic and biophysical studies have yielded somewhat conflicting results and an as yet unclear picture of the homotypic interactions of the cadherin extracellular domain during dimerization. To better understand the dynamics of cadherin interactions we have developed Fluorescence Resonance Energy Transfer (FRET) based sensors to monitor cadherin associations across cellular junctions in a dynamic manner in living cells.

Here, we demonstrate the functionality of FRET-based cadherin interaction reporters. FRET is unique in its ability to provide signals that are sensitive to changes in intra- or intermolecular distances in the 1-10 nm range, well below the inherent diffraction limit of conventional fluorescence microscopy. We believe that FRET is a powerful technique to monitor cadherin orientation and interactions in heterologous, living cells.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:cadherin; catenin; FRET; molecular neurobiology; synaptic plasticity
Degree Grantor:California Institute of Technology
Division:Biology
Major Option:Biology
Thesis Availability:Restricted to Caltech community only
Research Advisor(s):
  • Schuman, Erin Margaret
Thesis Committee:
  • Fraser, Scott E. (chair)
  • Schuman, Erin Margaret
  • Zinn, Kai George
  • Bjorkman, Pamela J.
Defense Date:30 November 2006
Record Number:CaltechETD:etd-02142007-004140
Persistent URL:http://resolver.caltech.edu/CaltechETD:etd-02142007-004140
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:633
Collection:CaltechTHESIS
Deposited By: Imported from ETD-db
Deposited On:30 May 2007
Last Modified:26 Dec 2012 02:31

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