Activity-Dependent Synaptogenesis: Regulation by a CaM-Kinase Kinase/CaM-Kinase I/βPIX Signaling Complex

Takeo Saneyoshi; Gary Wayman; Dale Fortin; Monika Davare; Naoto Hoshi; Naohito Nozaki; Tohru Natsume; Thomas R Soderling

doi:10.1016/j.neuron.2007.11.016

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Activity-Dependent Synaptogenesis: Regulation by a CaM-Kinase Kinase/CaM-Kinase I/βPIX Signaling Complex

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Activity-Dependent Synaptogenesis: Regulation by a CaM-Kinase Kinase/CaM-Kinase I/βPIX Signaling Complex

Takeo Saneyoshi, Gary Wayman, Dale Fortin, Monika Davare, Naoto Hoshi, Naohito Nozaki, Tohru Natsume and Thomas R Soderling

Neuron (Cambridge, Mass.), Vol.57(1), pp.94-107

01/10/2008

DOI: https://doi.org/10.1016/j.neuron.2007.11.016

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https://hdl.handle.net/2376/108673

PMCID: PMC2277504

PMID: 18184567

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https://doi.org/10.1016/j.neuron.2007.11.016View

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Abstract

CELLBIO

MOLNEURO

SIGNALING

Neuronal activity augments maturation of mushroom-shaped spines to form excitatory synapses, thereby strengthening synaptic transmission. We have delineated a Ca2+-signaling pathway downstream of the NMDA receptor that stimulates calmodulin-dependent kinase kinase (CaMKK) and CaMKI to promote formation of spines and synapses in hippocampal neurons. CaMKK and CaMKI form a multiprotein signaling complex with the guanine nucleotide exchange factor (GEF) βPIX and GIT1 that is localized in spines. CaMKI-mediated phosphorylation of Ser516 in βPIX enhances its GEF activity, resulting in activation of Rac1, an established enhancer of spinogenesis. Suppression of CaMKK or CaMKI by pharmacological inhibitors, dominant-negative (dn) constructs and siRNAs, as well as expression of the βPIX Ser516Ala mutant, decreases spine formation and mEPSC frequency. Constitutively-active Pak1, a downstream effector of Rac1, rescues spine inhibition by dnCaMKI or βPIX S516A. This activity-dependent signaling pathway can promote synapse formation during neuronal development and in structural plasticity.

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Title: Activity-Dependent Synaptogenesis: Regulation by a CaM-Kinase Kinase/CaM-Kinase I/βPIX Signaling Complex
Creators: Takeo Saneyoshi - Vollum Institute, Oregon Health and Sciences University, Portland, OR 97239, USA
Gary Wayman - Vollum Institute, Oregon Health and Sciences University, Portland, OR 97239, USA
Dale Fortin - Vollum Institute, Oregon Health and Sciences University, Portland, OR 97239, USA
Monika Davare - Vollum Institute, Oregon Health and Sciences University, Portland, OR 97239, USA
Naoto Hoshi - Vollum Institute, Oregon Health and Sciences University, Portland, OR 97239, USA
Naohito Nozaki - Kanagawa Dental College, Yokosuka, Kanagawa 238-8580, Japan
Tohru Natsume - National Institute of Advanced Industrial Science and Technology, Biological Information Research Center, Aomi, Tokyo 135-0064, Japan
Thomas R Soderling - Vollum Institute, Oregon Health and Sciences University, Portland, OR 97239, USA
Publication Details: Neuron (Cambridge, Mass.), Vol.57(1), pp.94-107
Academic Unit: Integrative Physiology and Neuroscience, Department of
Publisher: Elsevier Inc
Identifiers: 99900547118801842
Language: English
Resource Type: Journal article