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ICAM-5 affects spine maturation by regulation of NMDA receptor binding to α-actinin
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 metalloprote...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4365481/ https://www.ncbi.nlm.nih.gov/pubmed/25572420 http://dx.doi.org/10.1242/bio.201410439 |
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author | Ning, Lin Paetau, Sonja Nyman-Huttunen, Henrietta Tian, Li Gahmberg, Carl G. |
author_facet | Ning, Lin Paetau, Sonja Nyman-Huttunen, Henrietta Tian, Li Gahmberg, Carl G. |
author_sort | Ning, Lin |
collection | PubMed |
description | 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 α-actinin. We found that GluN1 and ICAM-5 partially compete for the binding to α-actinin; deletion of the cytoplasmic tail of ICAM-5 or ablation of the gene resulted in increased association of GluN1 with α-actinin, whereas internalization of ICAM-5 peptide perturbed the GluN1/α-actinin interaction. NMDA treatment decreased α-actinin binding to ICAM-5, and increased the binding to GluN1. Proper synaptic distribution of α-actinin requires the ICAM-5 cytoplasmic domain, without which α-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. |
format | Online Article Text |
id | pubmed-4365481 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The Company of Biologists |
record_format | MEDLINE/PubMed |
spelling | pubmed-43654812015-04-02 ICAM-5 affects spine maturation by regulation of NMDA receptor binding to α-actinin Ning, Lin Paetau, Sonja Nyman-Huttunen, Henrietta Tian, Li Gahmberg, Carl G. Biol Open Research Article 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 α-actinin. We found that GluN1 and ICAM-5 partially compete for the binding to α-actinin; deletion of the cytoplasmic tail of ICAM-5 or ablation of the gene resulted in increased association of GluN1 with α-actinin, whereas internalization of ICAM-5 peptide perturbed the GluN1/α-actinin interaction. NMDA treatment decreased α-actinin binding to ICAM-5, and increased the binding to GluN1. Proper synaptic distribution of α-actinin requires the ICAM-5 cytoplasmic domain, without which α-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. The Company of Biologists 2015-01-08 /pmc/articles/PMC4365481/ /pubmed/25572420 http://dx.doi.org/10.1242/bio.201410439 Text en © 2015. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Ning, Lin Paetau, Sonja Nyman-Huttunen, Henrietta Tian, Li Gahmberg, Carl G. ICAM-5 affects spine maturation by regulation of NMDA receptor binding to α-actinin |
title | ICAM-5 affects spine maturation by regulation of NMDA receptor binding to α-actinin |
title_full | ICAM-5 affects spine maturation by regulation of NMDA receptor binding to α-actinin |
title_fullStr | ICAM-5 affects spine maturation by regulation of NMDA receptor binding to α-actinin |
title_full_unstemmed | ICAM-5 affects spine maturation by regulation of NMDA receptor binding to α-actinin |
title_short | ICAM-5 affects spine maturation by regulation of NMDA receptor binding to α-actinin |
title_sort | icam-5 affects spine maturation by regulation of nmda receptor binding to α-actinin |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4365481/ https://www.ncbi.nlm.nih.gov/pubmed/25572420 http://dx.doi.org/10.1242/bio.201410439 |
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