Evolutionary conserved role for TARPs in the gating of glutamate receptors and tuning of synaptic function.
Neurotransmission in the brain is critically dependent on excitatory synaptic signaling mediated by AMPA-class ionotropic glutamate receptors (AMPARs). AMPARs are known to be associated with Transmembrane AMPA receptor Regulatory Proteins (TARPs). In vertebrates, at least four TARPs appear to have redundant roles as obligate chaperones for AMPARs, thus greatly complicating analysis of TARP participation in synaptic function. We have overcome this limitation by identifying and mutating the essential set of TARPs in C. elegans (STG-1 and STG-2). In TARP mutants, AMPAR-mediated currents and worm behaviors are selectively disrupted despite apparently normal surface expression and clustering of the receptors. Reconstitution experiments indicate that both STG-1 and STG-2 can functionally substitute for vertebrate TARPs to modify receptor function. Thus, we show that TARPs are obligate auxiliary subunits for AMPARs with a primary, evolutionarily conserved functional role in the modification of current kinetics.
Wang
Rui
R
Department of Biology, University of Utah, Salt Lake City, UT 84112-0840, USA.
Walker
Craig S
CS
Brockie
Penelope J
PJ
Francis
Michael M
MM
Mellem
Jerry E
JE
Madsen
David M
DM
Maricq
Andres V
AV
D000818:Animals; D030801:Animals, Genetically Modified; D001362:Avoidance Learning / Q000502:physiology*; D001483:Base Sequence; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D019143:Evolution, Molecular; D008564:Membrane Potentials / Q000502:physiology*; D026901:Membrane Transport Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid
D029742:Caenorhabditis elegans Proteins; D015220:Calcium Channels; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D018091:Receptors, AMPA; C512985:STG-1 protein, C elegans; C532436:STG-2 protein, C elegans; C096470:glr-1 protein, C elegans