Regulation of AMPA receptor trafficking by Rab6 and the retrograde transport pathway in Caenorhabditis elegans
Citation & Export
Hide
Simple citation
Zhang, Donglei.
Regulation of AMPA receptor trafficking by Rab6 and the retrograde transport pathway in Caenorhabditis elegans. Retrieved from
https://doi.org/doi:10.7282/T3CC0ZCTExport
Description
TitleRegulation of AMPA receptor trafficking by Rab6 and the retrograde transport pathway in Caenorhabditis elegans
Date Created2013
Other Date2013-01 (degree)
Extentxv, 293 p. : ill.
DescriptionRegulated membrane trafficking of AMPA-type glutamate receptors (AMPARs) is a key mechanism underlying synaptic plasticity, yet the pathways used by AMPARs are not well understood. Here we used gain and loss of function mutations combined with high resolution imaging of GLR-1 distribution in living neurons to show that the AMPAR subunit GLR-1 in C. elegans utilizes the retrograde transport pathway to regulate AMPAR synaptic abundance. Mutants for rab-6.2, rab-6.1, the retromer genes vps-35 and snx-1, and rme-8 failed to recycle GLR-1 receptors, resulting in GLR-1 turnover and behavioral defects indicative of diminished GLR-1 function. By contrast, expression of constitutively active RAB-6.2 and RAB-6.1 drove the retrograde transport of GLR-1 from dendrites back to cell body Golgi. We also find that the regulation of GLR-1 transport by RAB-6.2 required the activity of the PDZ/PTB domain protein LIN-10 as an effector. We show that the trafficking of MIG-14/Wntless protein, which undergoes retrograde recycling in the intestinal epithelia, is also regulated by RAB-6.2 and RAB-6.1. Colocalization studies show that in the absence of RAB-6.1 or RAB-6.2 function, MIG-14 cannot be transported to the Golgi, but is instead shunted to the lysosome. To better understand how RAB-6.2 regulates GLR-1 intracellular trafficking, we performed a yeast two-hybrid screen, using constitutively active RAB-6.2 (mutation Q69L) as the bait, to find novel RAB-6.2 interacting proteins. We have identified several candidates, which distribute into a variety of functional protein families, including motor proteins, coat proteins, vacuolar proton-translocating ATPase (v-ATPase) subunits, conserved oligomeric Golgi complex (COGC) subunits, and lipid phosphatases. In addition, we conducted an initial functional analysis to test whether these candidates have potential roles in the regulation of the retrograde trafficking pathway. Taken together, our results demonstrate a novel role for Rab6, its effectors, and the retromer complex in the regulation of AMPAR trafficking. This is the first demonstration that AMPAR trafficking is regulated by the retrograde transport pathway, and our findings provide a novel function for that transport pathway in maintaining synaptic strength.
NotePh.D.
NoteIncludes bibliographical references
NoteIncludes vita
Noteby Donglei Zhang
Genretheses, ETD doctoral
Languageeng
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
Statistical Profile