Cellular mechanisms that modulate kainate receptor trafficking and assembly

Show simple item record


dc.contributor.advisor Geoffrey T . Swanson en_US
dc.contributor.committeeMember Xiaodong Cheng en_US
dc.contributor.committeeMember Lisa A . Elferink en_US
dc.contributor.committeeMember Kenneth M . Johnson en_US
dc.contributor.committeeMember John Marshall en_US
dc.creator Pornpun Vivithanaporn en_US
dc.date.accessioned 2011 -12 -20T16 :05 :00Z
dc.date.accessioned 2014 -02 -19T22 :05 :23Z
dc.date.available 2008 -06 -17 en_US
dc.date.available 2011 -12 -20T16 :05 :00Z
dc.date.available 2014 -02 -19T22 :05 :23Z
dc.date.created 2007 -07 -20 en_US
dc.date.issued 2007 -06 -08 en_US
dc.identifier.other etd -07202007 -133932 en_US
dc.identifier.uri http : / /hdl .handle .net /2152 .3 /172
dc.description.abstract Kainate receptors (KARs ) in the mammalian brain play a variety of physiological roles that require selective assembly , intracellular trafficking , and synaptic targeting . Cytoplasmic and non -cytoplasmic determinants that modulate KAR expression at the plasma membrane have been recently characterized . The intracellular trafficking determinants are presumed to bind to chaperone proteins , but these proteins have not been identified for any KAR subunit . Here we identified two chaperone proteins that associated with the carboxy terminus but differently regulated the localization of KA2 receptors . We found that coatomer protein complex I (COPI ) subunits interacted with KA2 subunits at the arginine -based ER retention /retrieval motif and these associations were decreased in heteromeric GluR6a /KA2 receptors . Disruptions of COPI and KA2 associations by alanine mutations at the arginine -rich domain and elimination of COPI vesicles were correlated with the increased expression at the plasma membrane of KA2 receptors , indicating that COPI proteins regulated the ER localization of receptors . KA2 receptors also co -precipitated with three isoforms of 14 -3 -3 proteins ; only the KA2 and 14 -3 -3zeta association was correlated with higher plasma membrane expression of receptors . In addition to identifying cytoplasmic chaperone systems , we were interested in understanding the nature of a recently described trafficking checkpoint in non -cytoplasmic regions . Mutations in domains typically involved in glutamate binding and ion permeation disrupt expression of KARs at the plasma membrane . A conformational change of receptors after glutamate binding is proposed to permit egress of KARs from the ER . We mutated critical amino acid residues in the extracellular linker domain of GluR6a subunits and found that desensitization rates were only weakly correlated with plasma membrane expression levels . Alteration of these residues impaired other stages of receptor biosyntheis including assembly and degradation of mutated receptors . We found that mutations at the transduction linker collectively altered subunit assembly , degradation , desensitization and a post -assembly stage . Our characterizations of chaperone proteins and mechanisms that regulate intracellular trafficking provide a better understanding of cellular controls in the early stages of KAR biosynthesis . en_US
dc.format.medium electronic en_US
dc.language.iso eng en_US
dc.rights Copyright © is held by the author . Presentation of this material on the TDL web site by The University of Texas Medical Branch at Galveston was made possible under a limited license grant from the author who has retained all copyrights in the works . en_US
dc.subject plasma membrane expression en_US
dc.subject oligomerization en_US
dc.subject KA2 en_US
dc.subject glutamate receptors en_US
dc.subject GluR6 en_US
dc.subject biogenesis en_US
dc.title Cellular mechanisms that modulate kainate receptor trafficking and assembly en_US
dc.type.genre dissertation en_US
dc.type.material text en_US
thesis.degree.name PhD en_US
thesis.degree.level Doctoral en_US
thesis.degree.grantor The University of Texas Medical Branch en_US
thesis.degree.department Pharmacology and Toxicology en_US

Citation

Cellular mechanisms that modulate kainate receptor trafficking and assembly. Doctoral dissertation, The University of Texas Medical Branch. Available electronically from http : / /hdl .handle .net /2152 .3 /172 .

Files in this item

Files Size Format View
Dissertation-Vivithanaporn.pdf 27.85Mb application/pdf View/Open

This item appears in the following Collection(s)

Show simple item record

Search DSpace

Advanced Search

Browse