title: Temporal and spatial localization of nectin-1 and l-afadin during synaptogenesis in hippocampal neurons.
abstract: Nectins are cell adhesion molecules that, together with the intracellular binding partner afadin, mediate adhesion and signaling at a variety of intercellular junctions. In this work we studied the distribution of nectin-1 and afadin during hippocampal synapse formation using cultured primary hippocampal neurons. Nectin-1 and afadin cluster at developing synapses between hippocampal neurons. These nectin-afadin clusters uniformly colocalize with N-cadherin-catenin pairs, suggesting that formation of developing synapses involves participation of both bimolecular systems. Nectin-1 is initially expressed at excitatory and inhibitory synapses but is progressively lost at inhibitory synapses during their maturation. Treatment of neurons with actin depolymerizing agents disrupts the synaptically localized nectin-1 and afadin cluster at an early stage and elicits nectin-1 ectodomain shedding. These data indicate that the synaptic localization of nectin-1 and l-afadin are F-actin-dependent and that the shedding of nectin-1 is a mechanism contributing to synaptic plasticity.
authors.affiliation: Department of Neurology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
authors.forename: Seung T
authors.initials: ST
authors.lastname: Lim
authors.forename: Kuei-Cheng
authors.initials: KC
authors.lastname: Lim
authors.forename: Rita E
authors.initials: RE
authors.lastname: Giuliano
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Federoff
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000199:Actins / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D006624:Hippocampus / Q000196:embryology* / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D000075983:Nectins; D009433:Neural Inhibition / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology; D013997:Time Factors; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000199:Actins; C495267:CTNNB1 protein, mouse; D015820:Cadherins; C489083:Cdh2 protein, mouse; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; C000619015:Nectin1 protein, mouse; D000075983:Nectins; C108835:afadin; D051176:beta Catenin