TSPAN5 Enriched Microdomains Provide a Platform for Dendritic Spine Maturation through Neuroligin-1 Clustering
Cell Reports. 2019-10-01; 29(5): 1130-1146.e8
DOI: 10.1016/j.celrep.2019.09.051
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Moretto E(1), Longatti A(2), Murru L(3), Chamma I(4), Sessa A(5), Zapata J(3), Hosy E(4), Sainlos M(4), Saint-Pol J(6), Rubinstein E(6), Choquet D(7), Broccoli V(5), Schiavo G(8), Thoumine O(4), Passafaro M(9).
Author information:
(1)CNR, Institute of Neuroscience, Milan 20129, Italy; BioMETRA, Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy; UK Dementia Research Institute at University College London, London WC1E 6BT, UK.
(2)CNR, Institute of Neuroscience, Milan 20129, Italy; DiSFeB, Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy.
(3)CNR, Institute of Neuroscience, Milan 20129, Italy.
(4)Interdisciplinary Institute for Neuroscience, UMR 5297, Centre National de la Recherche Scientifique, Bordeaux, France; Interdisciplinary Institute for Neuroscience, University of Bordeaux, Bordeaux, France.
(5)Stem Cell and Neurogenesis Unit, Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy.
(6)INSERM, U935, 94807 Villejuif, France.
(7)Interdisciplinary Institute for Neuroscience, UMR 5297, Centre National de la Recherche Scientifique, Bordeaux, France; Interdisciplinary Institute for Neuroscience, University of Bordeaux, Bordeaux, France; Bordeaux Imaging Center, UMS3420, CNRS, University of Bordeaux, US4 INSERM, Bordeaux, France.
(8)UK Dementia Research Institute at University College London, London WC1E 6BT, UK; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK; Discoveries Centre for Regenerative and Precision Medicine, University College London Campus, London WC1N 3BG, UK.
(9)CNR, Institute of Neuroscience, Milan 20129, Italy. Electronic address: .
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.