title: IgLON cell adhesion molecules are shed from the cell surface of cortical neurons to promote neuronal growth.
abstract: Matrix metalloproteinases and a disintegrin and metalloproteinases are members of the zinc endopeptidases, which cleave components of the extracellular matrix as well as cell surface proteins resulting in degradation or release of biologically active fragments. Surface ectodomain shedding affects numerous biological processes, including survival, axon outgrowth, axon guidance, and synaptogenesis. In this study, we evaluated the role of metalloproteinases in regulating cortical neurite growth. We found that treatment of mature cortical neurons with pan-metalloproteinase inhibitors or with tissue inhibitors of metalloproteinase-3 reduced neurite outgrowth. Through mass spectrometry, we characterized the metalloproteinase-sensitive cell surface proteome of mature cortical neurons. Members of the IgLON family of glycosylphosphatidylinositol-anchored neural cell adhesion molecules were identified and validated as proteins that were shed from the surface of mature cortical neurons in a metalloproteinase-dependent manner. Introduction of two members of the IgLON family, neurotrimin and NEGR1, in early embryonic neurons was sufficient to confer sensitivity to metalloproteinase inhibitors in neurite outgrowth assays. Outgrowth experiments on immobilized IgLON proteins revealed a role for all IgLON family members in promoting neurite extension from cortical neurons. Together, our findings support a role for metalloproteinase-dependent shedding of IgLON family members in regulating neurite outgrowth from mature cortical neurons.
authors.affiliation: From the Department of Neurology and Neurosurgery, Montréal Neurological Institute, McGill University, Montréal, Québec H3A 2B4, Canada.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Sanz
authors.affiliation: From the Department of Neurology and Neurosurgery, Montréal Neurological Institute, McGill University, Montréal, Québec H3A 2B4, Canada.
authors.forename: Gino B
authors.initials: GB
authors.lastname: Ferraro
authors.affiliation: From the Department of Neurology and Neurosurgery, Montréal Neurological Institute, McGill University, Montréal, Québec H3A 2B4, Canada alyson.fournier@mcgill.ca.
authors.forename: Alyson E
authors.initials: AE
authors.lastname: Fournier
mesh_terms: D000818:Animals; D017209:Apoptosis; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D045726:Metalloproteases / Q000378:metabolism*; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D016501:Neurites / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D040901:Proteomics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D058851:GPI-Linked Proteins; D019006:Neural Cell Adhesion Molecules; C489215:Opcml protein, rat; D012333:RNA, Messenger; C095362:limbic system-associated membrane protein; C092530:neurotrimin; D045726:Metalloproteases
keywords: ADAM; Axon; Cell Adhesion; Matrix Metalloproteinase (MMP); Neuron; Shedding; Tissue Inhibitor of Metalloproteinase (TIMP)