title: Interaction of transmembrane AMPA receptor regulatory proteins with multiple membrane associated guanylate kinases.
abstract: Surface expression of AMPA type glutamate receptors requires stargazin or a related transmembrane AMPA receptor regulatory protein (TARP). Furthermore, interaction of the cytosolic tail of TARPs with PDZ domains of PSD-95 targets AMPA receptors to postsynaptic densities. Here, we screened for additional proteins that might interact with the cytosolic domain of TARPs. Screening a rat brain cDNA library with the yeast two-hybrid system yielded six PDZ proteins that can bind tail of TARPs. These PDZ proteins include the four neuronal membrane associated guanylate kinases, PSD-95/SAP-90, PSD-93/Chapsyn-110, SAP-97/hDLG and SAP-102; the multi-PDZ protein, MUPP1; and the mitochondrial PDZ protein, OMP-25. Although all of these proteins can bind to TARPs in vitro, only two of these, PSD-95 and PSD-93 associate with TARPs in brain. We also found that all three PDZ domains from PSD-95 associate with the TARP C-termini with similar affinities. This work identifies biochemical promiscuity for interaction of the TARP C-termini with PDZ domains in vitro, but also shows that only specific synaptic PDZ proteins associate with TARPs in brain.
authors.affiliation: Department of Physiology, UCSF School of Medicine, University of California at San Francisco, Genentech Hall 600 16th Street, N272-F, San Francisco, CA 94143-2140, USA.
authors.forename: Srikanth
authors.initials: S
authors.lastname: Dakoji
authors.forename: Susumu
authors.initials: S
authors.lastname: Tomita
authors.forename: Siavash
authors.initials: S
authors.lastname: Karimzadegan
authors.forename: Roger A
authors.initials: RA
authors.lastname: Nicoll
authors.forename: David S
authors.initials: DS
authors.lastname: Bredt
mesh_terms: D000818:Animals; D019556:COS Cells; D015220:Calcium Channels / Q000378:metabolism; D002522:Chlorocebus aethiops; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D018091:Receptors, AMPA / Q000378:metabolism*
chemical_list: C491911:Cacng2 protein, rat; D015220:Calcium Channels; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C501451:Mpp2 protein, rat; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; C033652:postsynaptic density proteins; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases