Compensatory redistribution of neuroligins and N-cadherin following deletion of synaptic β1-integrin

Steven Mortillo, Alice Elste, Yongchao Ge, Shekhar B. Patil, Kuangfu Hsiao, George W. Huntley, Ronald L. Davis, Deanna L. Benson

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

β1-containing integrins are required for persistent synaptic potentiation in hippocampus and regulate hippocampal-dependent learning. Based largely on indirect evidence, there is a prevailing assumption that β1-integrins are localized at synapses, where they contribute to synapse adhesion and signaling, but this has not been examined directly. Here we investigate the fine localization of β1-integrin in adult mouse hippocampus using high-resolution immunogold labeling, with a particular emphasis on synaptic labeling patterns. We find that β1-integrins localize to synapses in CA1 and are concentrated postsynaptically. At the postsynaptic membrane, β1-integrins are found more commonly clustered near active zone centers rather than at the peripheral edges. In mice harboring a conditional deletion of β1-integrins, labeling for N-cadherin and neuroligins increases. Western blots show increased levels of N-cadherin in total lysates and neuroligins increase selectively in synaptosomes. These data suggest there is a dynamic, compensatory adjustment of synaptic adhesion. Such adjustment is specific only for certain cell adhesion molecules (CAMs), because labeling for SynCAM is unchanged. Together, our findings demonstrate unequivocally that β1-integrin is an integral synaptic adhesion protein, and suggest that adhesive function at the synapse reflects a cooperative and dynamic network of multiple CAM families.

Original languageEnglish
Pages (from-to)2041-2052
Number of pages12
JournalJournal of Comparative Neurology
Volume520
Issue number9
DOIs
StatePublished - 15 Jun 2012

Keywords

  • CAMs
  • Cadherin
  • Neuroligins
  • SynCAM
  • Synapse specificity
  • Synaptic cell adhesion molecules
  • Synaptic cleft

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