Interactions between Intercellular Adhesion Molecule-5 (ICAM-5) and β1 integrins regulate neuronal synapse formation.

Lin Ning, Li Tian, Sergei Smirnov, Helena Vihinen, Olaya Llano Sanchez, Kyle Vick, Ronald L. Davis, Claudio Rivera Baeza, Carl G. Gahmberg

Research output: Contribution to journalArticleScientificpeer-review


ICAM-5 is a dendrite-specific adhesion molecule, which functions in both the immune and nervous systems. ICAM-5 is the only identified negative regulator for spine maturation so far. Shedding of ICAM-5 ectodomain leads to promoted spine maturation and enhanced synaptic activity. However, the mechanism by which ICAM-5 regulates spine development remains poorly understood. In this study, we found that ablation of ICAM5 expression resulted in a significant increase in the formation of synaptic contacts and the frequency of miniature excitatory postsynaptic currents, an indicator of pre-synaptic release probability. Antibodies against ICAM-5 and β1 integrins altered spine maturation. Furthermore we found that β1 integrins serve as binding partners for ICAM-5. β1 integrins were immune precipitated with ICAM-5 from mouse brain and the binding region in ICAM-5 was localized to the two first Ig-domains. β1 integrins were juxtaposed to filopodia tips at the early stage of synaptic formation, but as synapses matured, β1 integrins covered the mushroom spines. Loss of β1 integrins from the pre-synaptic sites affected the morphology of the post-synaptic structures. ICAM-5 ectodomain cleavage decreased or increased respectively, when the interaction between ICAM-5 and β1 integrins was potentiated or weakened using antibodies. These results suggest that the interaction between ICAM-5 and β1 integrins plays an important role in formation of functional synapses.
Original languageEnglish
JournalJournal of Cell Science
Issue number1
Pages (from-to)77-89
Number of pages13
Publication statusPublished - 2013
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 1184 Genetics, developmental biology, physiology
  • dendritic spine
  • synapse formation

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