Ning , L , Paetau , S , Nyman-Huttunen , H , Tian , L & Gahmberg , C G 2015 , ' ICAM-5 affects spine maturation by regulation of NMDA receptor binding to alpha-actinin ' , Biology open , vol. 4 , no. 2 , pp. 125-136 . https://doi.org/10.1242/bio.201410439
Title: | ICAM-5 affects spine maturation by regulation of NMDA receptor binding to alpha-actinin |
Author: | Ning, Lin; Paetau, Sonja; Nyman-Huttunen, Henrietta; Tian, Li; Gahmberg, Carl G. |
Contributor organization: | Biosciences Biochemistry and Biotechnology Faculty of Biological and Environmental Sciences Neuroscience Center Gahmberg Group |
Date: | 2015-02-15 |
Language: | eng |
Number of pages: | 12 |
Belongs to series: | Biology open |
ISSN: | 2046-6390 |
DOI: | https://doi.org/10.1242/bio.201410439 |
URI: | http://hdl.handle.net/10138/166636 |
Abstract: | ICAM-5 is a negative regulator of dendritic spine maturation and facilitates the formation of filopodia. Its absence results in improved memory functions, but the mechanisms have remained poorly understood. Activation of NMDA receptors induces ICAM-5 ectodomain cleavage through a matrix metalloproteinase (MMP)-dependent pathway, which promotes spine maturation and synapse formation. Here, we report a novel, ICAM-5-dependent mechanism underlying spine maturation by regulating the dynamics and synaptic distribution of a-actinin. We found that GluN1 and ICAM-5 partially compete for the binding to alpha-actinin; deletion of the cytoplasmic tail of ICAM-5 or ablation of the gene resulted in increased association of GluN1 with alpha-actinin, whereas internalization of ICAM-5 peptide perturbed the GluN1/alpha-actinin interaction. NMDA treatment decreased alpha-actinin binding to ICAM-5, and increased the binding to GluN1. Proper synaptic distribution of alpha-actinin requires the ICAM-5 cytoplasmic domain, without which alpha-actinin tended to accumulate in filopodia, leading to F-actin reorganization. The results indicate that ICAM-5 retards spine maturation by preventing reorganization of the actin cytoskeleton, but NMDA receptor activation is sufficient to relieve the brake and promote the maturation of spines. |
Subject: |
ICAM-5
Integrin Actinin Cell adhesion Spine maturation LONG-TERM POTENTIATION DENDRITIC SPINES NEURONAL GLYCOPROTEIN ADHESION MOLECULE TELENCEPHALIN PROTEIN MORPHOGENESIS LOCALIZATION ACTIVATION PLASTICITY 1182 Biochemistry, cell and molecular biology |
Peer reviewed: | Yes |
Rights: | cc_by |
Usage restriction: | openAccess |
Self-archived version: | publishedVersion |
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