title: Ectodomain shedding of nectin-1 regulates the maintenance of dendritic spine density.
abstract: Synaptic remodeling has been postulated as a mechanism underlying synaptic plasticity and cell adhesion molecules are thought to contribute to this process. We examined the role of nectin-1 ectodomain shedding on synaptogenesis in cultured rat hippocampal neurons. Nectins are Ca(2+) -independent immunoglobulin-like adhesion molecules, involved in cell-cell adherens junctions. Herein, we show that the processing of nectin-1 occurs by multiple endoproteolytic steps both in vivo and in vitro. We identified regions containing two distinct cleavage sites within the ectodomain of nectin-1. By alanine scanning mutagenesis, two point mutations that disrupt nectin-1 ectodomain cleavage events were identified. Expression of these mutants significantly alters the density of dendritic spines. These findings suggest that ectodomain shedding of nectin-1 regulates dendritic spine density and related synaptic functions.
authors: Neuroscience Department, Georgetown University Medical Center, Washington, District of Columbia 20057, USA.
authors: Seung T
authors: ST
authors: Lim
authors: Allison
authors: A
authors: Chang
authors: Rita E
authors: RE
authors: Giuliano
authors: Howard J
authors: HJ
authors: Federoff
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003712:Dendrites / Q000648:ultrastructure*; D049229:Dendritic Spines / Q000502:physiology* / Q000648:ultrastructure; D004622:Embryo, Mammalian; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D000075983:Nectins; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D017354:Point Mutation / Q000235:genetics; D011247:Pregnancy; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014161:Transduction, Genetic; D014162:Transfection
chemical_list: D015815:Cell Adhesion Molecules; C000619010:NECTIN1 protein, human; C000619015:Nectin1 protein, mouse; D000075983:Nectins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D053829:Amyloid Precursor Protein Secretases