Integrin β1 Signals through Arg to Regulate Postnatal Dendritic Arborization, Synapse Density, and Behavior
Year: 2012
Type: article
Abstract: Integrins are heterodimeric extracellular matrix receptors that are essential for the proper development of the vertebrate nervous system. We report here that selective loss of integrin β1 in excitatory neurons leads to reductions in the size and complexity of hippocampal dendritic arbors, hippocampal synapse loss, impaired hippocampus-dependent learning, and exaggerated psychomotor sensitivity to cocaine in mice. Our biochemical and genetic experiments demonstrate that the intracellular tail of integrin β1 binds directly to Arg kinase and that this interaction stimulates activity of the Arg substrate p190RhoGAP, an inactivator of the RhoA GTPase. Moreover, genetic manipulations that reduce integrin β1 signaling through Arg recapitulate the integrin β1 knock-out phenotype in a gene dose-sensitive manner. Together, these results describe a novel integrin β1-Arg-p190RhoGAP pathway that regulates dendritic arbor size, promotes synapse maintenance, supports proper hippocampal function, and mitigates the behavioral consequences of cocaine exposure.
Source: Journal of Neuroscience
Institutions: Yale University, University of California, San Francisco
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Funders: American Heart Association, U.S. Public Health Service, National Institute on Alcohol Abuse and Alcoholism, National Institute on Aging, National Institute on Drug Abuse, National Cancer Institute, National Institute on Deafness and Other Communication Disorders, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke
Awards: SPOKEN WORD RECOGNITION USING VISUALLY MEDIATED TASKS, The mechanism of Arg kinase activation by integrin B1, Predoctoral Program in Cellular and Molecular Biology, Genetic Determinants of Local Circuit Organization, Integrin Signaling in Nervous System Development, G4141023946, Integrin Signaling Through Arg Kinase Regulates Synapse, Dendrite Stabilization, Stress-Induced Compulsive Behaviors: CRF Regulation (#3 of 14), Regulation of dendritic spine shape and synapse and dendrite stability by Arg, Cognitive Dysfunction after Chronic Cocaine, Regulation of Invadopodia Formation in Breast Cancer Cells, Adhesion-dependent inhibition of RhoA through Arg tyrosine kinase and p190RhoGAP, Incentive Motivation and Addiction: PKA Mechanisms
OpenAlex ID: W1998123755