@article{1180edea97374c9f9ab5a350b5589921,
title = "Kalirin-7 Controls Activity-Dependent Structural and Functional Plasticity of Dendritic Spines",
abstract = "Activity-dependent rapid structural and functional modifications of central excitatory synapses contribute to synapse maturation, experience-dependent plasticity, and learning and memory and are associated with neurodevelopmental and psychiatric disorders. However, the signal transduction mechanisms that link glutamate receptor activation to intracellular effectors that accomplish structural and functional plasticity are not well understood. Here we report that NMDA receptor activation in pyramidal neurons causes CaMKII-dependent phosphorylation of the guanine-nucleotide exchange factor (GEF) kalirin-7 at residue threonine 95, regulating its GEF activity, leading to activation of small GTPase Rac1 and rapid enlargement of existing spines. Kalirin-7 also interacts with AMPA receptors and controls their synaptic expression. By demonstrating that kalirin expression and spine localization are required for activity-dependent spine enlargement and enhancement of AMPAR-mediated synaptic transmission, our study identifies a signaling pathway that controls structural and functional spine plasticity.",
keywords = "CELLBIO, MOLNEURO, SIGNALING",
author = "Zhong Xie and Srivastava, {Deepak P.} and Huzefa Photowala and Li Kai and Cahill, {Michael E.} and Woolfrey, {Kevin M.} and Shum, {Cassandra Y.} and Surmeier, {D. James} and Peter Penzes",
note = "Funding Information: We thank Dr. Richard L. Huganir (Johns Hopkins Univ.) for the GluR1 and NR2A polyclonal antibodies; Dr. Dane Chetkovich and Ms. Emma Hayes (Northwestern Univ.) for assistance with phosphorylation assays; Dr. Tobias Meyer (Stanford Univ.) for CaMKII expression plasmids; Dr. Gary G. Borisy and Dr. Shin-ichiro Kojima (Northwestern Univ.) for the pGsuper plasmid and assistance with RNAi; Dr. Gordon Shepherd for reading the manuscript (Northwestern Univ.); Dr. Anis Contractor (Northwestern Univ.) and Dr. Suzanne Zukin (Albert Einstein College of Medicine) for useful discussions; Dr. David Wokosin, and Dr. Jaime Grutzendler (Northwestern Univ.) for advice on image quantification; Dr. Jack Waters (Northwestern Univ.) for help with confocal measurements; and Ms. Kelly Jones for careful editing. This work was supported by the NIH-NIMH (MH071316), NAAR, NARSAD (to P.P.), and NIH-NINDS (to D.J.S.). ",
year = "2007",
month = nov,
day = "21",
doi = "10.1016/j.neuron.2007.10.005",
language = "English",
volume = "56",
pages = "640--656",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "4",
}