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...
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2015-01-01
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| Series: | Biology Open |
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| Online Access: | http://bio.biologists.org/content/4/2/125 |
| _version_ | 1818734497357627392 |
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| author | Lin Ning Sonja Paetau Henrietta Nyman-Huttunen Li Tian Carl G. Gahmberg |
| author_facet | Lin Ning Sonja Paetau Henrietta Nyman-Huttunen Li Tian Carl G. Gahmberg |
| author_sort | Lin Ning |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-18T00:06:18Z |
| format | Article |
| id | doaj.art-586db7d012904c92878ae1bfe0be8c65 |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-18T00:06:18Z |
| publishDate | 2015-01-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-586db7d012904c92878ae1bfe0be8c652022-12-21T21:27:47ZengThe Company of BiologistsBiology Open2046-63902015-01-014212513610.1242/bio.201410439201410439ICAM-5 affects spine maturation by regulation of NMDA receptor binding to α-actininLin Ning0Sonja Paetau1Henrietta Nyman-Huttunen2Li Tian3Carl G. Gahmberg4 Division of Biochemistry and Biotechnology, Faculty of Biological and Environmental Sciences, University of Helsinki, Viikinkaari 5, FIN-00014, Helsinki, Finland Division of Biochemistry and Biotechnology, Faculty of Biological and Environmental Sciences, University of Helsinki, Viikinkaari 5, FIN-00014, Helsinki, Finland Division of Biochemistry and Biotechnology, Faculty of Biological and Environmental Sciences, University of Helsinki, Viikinkaari 5, FIN-00014, Helsinki, Finland Neuroscience Center, University of Helsinki, Viikinkaari 4, FIN-00014, Helsinki, Finland Division of Biochemistry and Biotechnology, Faculty of Biological and Environmental Sciences, University of Helsinki, Viikinkaari 5, FIN-00014, Helsinki, Finland 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.http://bio.biologists.org/content/4/2/125ICAM-5IntegrinActininCell adhesionSpine maturation |
| spellingShingle | Lin Ning Sonja Paetau Henrietta Nyman-Huttunen Li Tian Carl G. Gahmberg ICAM-5 affects spine maturation by regulation of NMDA receptor binding to α-actinin Biology Open ICAM-5 Integrin Actinin Cell adhesion Spine maturation |
| 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 | ICAM-5 Integrin Actinin Cell adhesion Spine maturation |
| url | http://bio.biologists.org/content/4/2/125 |
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