α5 integrin signaling regulates the formation of spines and synapses in hippocampal neurons

Donna J. Webb, Huaye Zhang, Devi Majumdar, Alan F. Horwitz

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

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 α5 integrin regulates spine morphogenesis and synapse formation in hippocampal neurons. Knockdown of α5 integrin expression using small interfering RNA decreased the number of dendritic protrusions, spines, and synapses. Expression of constitutively active or dominant negative α5 integrin also resulted in alterations in the number of dendritic protrusions, spines, and synapses. α5 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.

Original languageEnglish (US)
Pages (from-to)6929-6935
Number of pages7
JournalJournal of Biological Chemistry
Volume282
Issue number10
DOIs
StatePublished - Mar 2 2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'α5 integrin signaling regulates the formation of spines and synapses in hippocampal neurons'. Together they form a unique fingerprint.

Cite this