title: Kalirin and Trio proteins serve critical roles in excitatory synaptic transmission and LTP.
abstract: The molecular mechanism underlying long-term potentiation (LTP) is critical for understanding learning and memory. CaMKII, a key kinase involved in LTP, is both necessary and sufficient for LTP induction. However, how CaMKII gives rise to LTP is currently unknown. Recent studies suggest that Rho GTPases are necessary for LTP. Rho GTPases are activated by Rho guanine exchange factors (RhoGEFs), but the RhoGEF(s) required for LTP also remain unknown. Here, using a combination of molecular, electrophysiological, and imaging techniques, we show that the RhoGEF Kalirin and its paralog Trio play critical and redundant roles in excitatory synapse structure and function. Furthermore, we show that CaMKII phosphorylation of Kalirin is sufficient to enhance synaptic AMPA receptor expression, and that preventing CaMKII signaling through Kalirin and Trio prevents LTP induction. Thus, our data identify Kalirin and Trio as the elusive targets of CaMKII phosphorylation responsible for AMPA receptor up-regulation during LTP.
authors: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143;
authors: Bruce E
authors: BE
authors: Herring
authors: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143; Department of Physiology, University of California, San Francisco, CA 94143 nicoll@cmp.ucsf.edu.
authors: Roger A
authors: RA
authors: Nicoll
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000502:physiology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D055785:Gene Knockdown Techniques; D055786:Gene Knockout Techniques; D020662:Guanine Nucleotide Exchange Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology*; D051379:Mice; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C548820:KALRN protein, mouse; C102365:Kalrn protein, rat; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C490975:Trio protein, mouse; C500736:Trio protein, rat; D017346:Protein Serine-Threonine Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
keywords: CaMKII; Kalirin; LTP; Trio; spines