Selective regulation of long-form calcium-permeable AMPA receptors by an atypical TARP, gamma-5.
Although the properties and trafficking of AMPA-type glutamate receptors (AMPARs) depend critically on associated transmembrane AMPAR regulatory proteins (TARPs) such as stargazin (gamma-2), no TARP has been described that can specifically regulate the important class of calcium-permeable (CP-) AMPARs. We examined the stargazin-related protein gamma-5, which is highly expressed in Bergmann glia, a cell type possessing only CP-AMPARs. gamma-5 was previously thought not to be a TARP, and it has been widely used as a negative control. Here we find that, contrary to expectation, gamma-5 acts as a TARP and serves this role in Bergmann glia. Whereas gamma-5 interacts with all AMPAR subunits, and modifies their behavior to varying extents, its main effect is to regulate the function of AMPAR subunit combinations that lack short-form subunits, which constitute predominantly CP-AMPARs. Our results suggest an important role for gamma-5 in regulating the functional contribution of CP-AMPARs.
Soto
David
D
Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
Coombs
Ian D
ID
Renzi
Massimiliano
M
Zonouzi
Marzieh
M
Farrant
Mark
M
Cull-Candy
Stuart G
SG
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000502:physiology; D020013:Calcium Signaling / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009457:Neuroglia / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D021381:Protein Transport / Q000235:genetics; D051381:Rats; D018091:Receptors, AMPA / Q000145:classification* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
C491911:Cacng2 protein, rat; C532434:Cacng5 protein, rat; D015220:Calcium Channels; D020033:Protein Isoforms; D018091:Receptors, AMPA; D002118:Calcium