TSPAN5 Enriched Microdomains Provide a Platform for Dendritic Spine Maturation through Neuroligin-1 Clustering
| Autor: | Vania Broccoli, Olivier Thoumine, Ingrid Chamma, Giampietro Schiavo, Julien Saint-Pol, Eric Rubinstein, Jonathan Zapata, Edoardo Moretto, Maria Passafaro, Daniel Choquet, Alessandro Sessa, Eric Hosy, Matthieu Sainlos, Luca Murru, Anna Longatti |
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| Přispěvatelé: | Interdisciplinary Institute for Neuroscience (IINS), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Modèles de Cellules Souches Malignes et Thérapeutiques, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut André Lwoff - Biologie intégrée de la cellule, virus et cancer (IALBICVC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Physiologie cellulaire de la synapse (PCS), Université Bordeaux Segalen - Bordeaux 2-Institut François Magendie-Centre National de la Recherche Scientifique (CNRS), San Raffaele Scientific Institute, Vita-Salute San Raffaele University and Center for Translational Genomics and Bioinformatics, Molecular Neuropathology Laboratory, Cancer Research UK London Research Institute, Pharmacology, Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Dendritic spine MESH: Hippocampus Tetraspanins TSPAN5 MESH: Membrane Microdomains Neuroligin Hippocampus MESH: Synapses 0302 clinical medicine Tetraspanin Postsynaptic potential neuroligin-1 MESH: Animals lcsh:QH301-705.5 ComputingMilieux_MISCELLANEOUS MESH: Cell Adhesion Molecules Neuronal Gene knockdown [SDU.ASTR]Sciences of the Universe [physics]/Astrophysics [astro-ph] Pyramidal Cells Compartmentalization (psychology) Transmembrane protein Cell biology Gene Knockdown Techniques MESH: HEK293 Cells embryonic structures Excitatory postsynaptic potential [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Protein Binding clustering Cell Adhesion Molecules Neuronal Biology General Biochemistry Genetics and Molecular Biology Article MESH: Dendritic Spines 03 medical and health sciences Membrane Microdomains MESH: Mice Inbred C57BL Animals Humans MESH: Protein Binding Rats Wistar MESH: Humans dendritic spines MESH: Pyramidal Cells MESH: Rats Wistar MESH: Gene Knockdown Techniques Mice Inbred C57BL 030104 developmental biology HEK293 Cells tetraspanin lcsh:Biology (General) MESH: HeLa Cells TEMs synapses MESH: Tetraspanins 030217 neurology & neurosurgery HeLa Cells |
| Zdroj: | Cell Reports Cell Reports, Elsevier Inc, 2019, 29 (5), pp.1130-1146.e8. ⟨10.1016/j.celrep.2019.09.051⟩ Cell Reports, Vol 29, Iss 5, Pp 1130-1146.e8 (2019) |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2019.09.051⟩ |
| Popis: | Summary Tetraspanins are a class of evolutionarily conserved transmembrane proteins with 33 members identified in mammals that have the ability to organize specific membrane domains, named tetraspanin-enriched microdomains (TEMs). Despite the relative abundance of different tetraspanins in the CNS, few studies have explored their role at synapses. Here, we investigate the function of TSPAN5, a member of the tetraspanin superfamily for which mRNA transcripts are found at high levels in the mouse brain. We demonstrate that TSPAN5 is localized in dendritic spines of pyramidal excitatory neurons and that TSPAN5 knockdown induces a dramatic decrease in spine number because of defects in the spine maturation process. Moreover, we show that TSPAN5 interacts with the postsynaptic adhesion molecule neuroligin-1, promoting its correct surface clustering. We propose that membrane compartmentalization by tetraspanins represents an additional mechanism for regulating excitatory synapses. Graphical Abstract Highlights • TSPAN5 is expressed in pyramidal neurons and localizes mainly to dendritic spines • TSPAN5 interacts with neuroligin-1 and promotes its clustering • TSPAN5-neuroligin-1 complex is fundamental for dendritic spine maturation Moretto et al. demonstrate that TSPAN5 controls the maturation of dendritic spines by promoting the clustering of neuroligin-1. These findings provide proof of principle that compartmentalization of transmembrane proteins through tetraspanins can represent an additional level of regulation of synapse formation and function. |
| Databáze: | OpenAIRE |
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