alpha5 integrin signaling regulates the formation of spines and synapses in hippocampal neurons.

Webb DJ, Zhang H, Majumdar D, Horwitz AF
J Biol Chem. 2007 282 (10): 6929-35

PMID: 17213186 · PMCID: PMC2750863 · DOI:10.1074/jbc.M610981200

The actin-based dynamics of dendritic spines play a key role in synaptic plasticity, which underlies learning and memory. Although it is becoming increasingly clear that modulation of actin is critical for spine dynamics, the upstream molecular signals that regulate the formation and plasticity of spines are poorly understood. In non-neuronal cells, integrins are critical modulators of the actin cytoskeleton, but their function in the nervous system is not well characterized. Here we show that alpha5 integrin regulates spine morphogenesis and synapse formation in hippocampal neurons. Knockdown of alpha5 integrin expression using small interfering RNA decreased the number of dendritic protrusions, spines, and synapses. Expression of constitutively active or dominant negative alpha5 integrin also resulted in alterations in the number of dendritic protrusions, spines, and synapses. alpha5 integrin signaling regulates spine morphogenesis and synapse formation by a mechanism that is dependent on Src kinase, Rac, and the signaling adaptor GIT1. Alterations in the activity or localization of these molecules result in a significant decrease in the number of spines and synapses. Thus, our results point to a critical role for integrin signaling in regulating the formation of dendritic spines and synapses in hippocampal neurons.

MeSH Terms (13)

Animals Cell Cycle Proteins Cells, Cultured Dendrites Hippocampus Integrin alpha5 Morphogenesis Phosphoproteins Proto-Oncogene Proteins c-akt Rats Signal Transduction src-Family Kinases Synapses

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