title: Neuroligin 1 induces blood vessel maturation by cooperating with the α6 integrin.
abstract: The synaptic protein Neuroligin 1 (NLGN1), a cell adhesion molecule, is critical for the formation and consolidation of synaptic connectivity and is involved in vascular development. The mechanism through which NLGN1 acts, especially in vascular cells, is unknown. Here, we aimed at deepening our knowledge on the cellular activities and molecular pathways exploited by endothelial NLGN1 both in vitro and in vivo. We analyzed the phenotypic consequences of NLGN1 expression modulation in endothelial cells through in vitro angiogenesis assays and the mouse postnatal retinal angiogenesis model. We demonstrate that NLGN1, whereas not affecting endothelial cell proliferation or migration, modulates cell adhesion to the vessel stabilizing protein laminin through cooperation with the α6 integrin, a specific laminin receptor. Finally, we show that in vivo, NLGN1 and α6 integrin preferentially colocalize in the mature retinal vessels, whereas NLGN1 deletion causes an aberrant VE-cadherin, laminin and α6 integrin distribution in vessels, along with significant structural defects in the vascular tree.
authors.affiliation: From the Department of Oncology, University of Torino Medical School, Laboratory of Neurovascular Biology.
authors.forename: Anna Valeria
authors.initials: AV
authors.lastname: Samarelli
authors.affiliation: From the Department of Oncology, University of Torino Medical School, Laboratory of Neurovascular Biology.
authors.forename: Elena
authors.initials: E
authors.lastname: Riccitelli
authors.affiliation: From the Department of Oncology, University of Torino Medical School, Laboratory of Neurovascular Biology.
authors.forename: Laura
authors.initials: L
authors.lastname: Bizzozero
authors.affiliation: From the Department of Oncology, University of Torino Medical School, Laboratory of Neurovascular Biology.
authors.forename: Tatiana Nunes
authors.initials: TN
authors.lastname: Silveira
authors.affiliation: From the Department of Oncology, University of Torino Medical School, Cell Migration.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Seano
authors.affiliation: From the Department of Oncology, University of Torino Medical School, Laboratory of Neurovascular Biology.
authors.forename: Margherita
authors.initials: M
authors.lastname: Pergolizzi
authors.affiliation: From the Department of Oncology, University of Torino Medical School, Laboratory of Neurovascular Biology.
authors.forename: Grazia
authors.initials: G
authors.lastname: Vitagliano
authors.affiliation: the Laboratoire CRRET, Faculté des Sciences et Technologie, Université Paris Est Créteil Val de Marne, 61 avenue du Général de Gaulle, 94010 Créteil Cedex, France.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cascone
authors.affiliation: the Laboratoire CRRET, Faculté des Sciences et Technologie, Université Paris Est Créteil Val de Marne, 61 avenue du Général de Gaulle, 94010 Créteil Cedex, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Carpentier
authors.affiliation: From the Department of Oncology, University of Torino Medical School, Laboratory of Neurovascular Biology.
authors.forename: Alessia
authors.initials: A
authors.lastname: Bottos
authors.affiliation: From the Department of Oncology, University of Torino Medical School, Cell Migration.
authors.forename: Luca
authors.initials: L
authors.lastname: Primo
authors.affiliation: From the Department of Oncology, University of Torino Medical School, Vascular Oncology, Candiolo Cancer Institute,10060 Candiolo, Torino Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Bussolino
authors.affiliation: From the Department of Oncology, University of Torino Medical School and Laboratory of Neurovascular Biology, Candiola Cancer Institute,10060 Candiola, Torino, Italy. marco.arese@ircc.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Arese
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D039503:Integrin alpha6 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D018919:Neovascularization, Physiologic / Q000502:physiology*; D012171:Retinal Vessels / Q000166:cytology / Q000378:metabolism*; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D015816:Cell Adhesion Molecules, Neuronal; D039503:Integrin alpha6; D000099152:Cadherin 5; C588002:ITGA6 protein, human; C093438:neuroligin 1
keywords: Angiogenesis; Blood Vessel Maturation; Cell Adhesion; Extracellular Matrix; Integrin; Laminin