title: MT5-MMP regulates adult neural stem cell functional quiescence through the cleavage of N-cadherin.
abstract: The identification of mechanisms that maintain stem cell niche architecture and homeostasis is fundamental to our understanding of tissue renewal and repair. Cell adhesion is a well-characterized mechanism for developmental morphogenetic processes, but its contribution to the dynamic regulation of adult mammalian stem cell niches is still poorly defined. We show that N-cadherin-mediated anchorage of neural stem cells (NSCs) to ependymocytes in the adult murine subependymal zone modulates their quiescence. We further identify MT5-MMP as a membrane-type metalloproteinase responsible for the shedding of the N-cadherin ectodomain in this niche. MT5-MMP is co-expressed with N-cadherin in adult NSCs and ependymocytes and, whereas MT5-MMP-mediated cleavage of N-cadherin is dispensable for the regulation of NSC generation and identity, it is required for proper activation of NSCs under physiological and regenerative conditions. Our results indicate that the proliferative status of stem cells can be dynamically modulated by regulated cleavage of cell adhesion molecules.
authors: 1] Centro de Investigaciones Biomédicas en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 28049 Madrid, Spain [2] Departamento de Biología Celular, Universidad de Valencia, 46100 Valencia, Spain [3] Cell Division and Cancer Group, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
authors: Eva
authors: E
authors: Porlan
authors: 1] Centro de Investigaciones Biomédicas en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 28049 Madrid, Spain [2] Departamento de Biología Celular, Universidad de Valencia, 46100 Valencia, Spain.
authors: Beatriz
authors: B
authors: Martí-Prado
authors: 1] Centro de Investigaciones Biomédicas en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 28049 Madrid, Spain [2] Departamento de Biología Celular, Universidad de Valencia, 46100 Valencia, Spain.
authors: José Manuel
authors: JM
authors: Morante-Redolat
authors: 1] Institut de Biomedicina de la Universitat de Barcelona, (IBUB), 08028 Barcelona, Spain [2] Department of Biomedical Sciences and Biotechnologies, University of Brescia and National Institute of Neuroscience, 25123 Brescia, Italy.
authors: Antonella
authors: A
authors: Consiglio
authors: 1] Centro de Investigaciones Biomédicas en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 28049 Madrid, Spain [2] Departamento de Biología Celular, Universidad de Valencia, 46100 Valencia, Spain.
authors: Ana C
authors: AC
authors: Delgado
authors: Cic BioGUNE, Parque Tecnológico de Vizcaya, 48160 Derio, Spain.
authors: Robert
authors: R
authors: Kypta
authors: Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Oncología (IUOPA), Universidad de Oviedo, 33006 Oviedo, Spain.
authors: Carlos
authors: C
authors: López-Otín
authors: 1] Centro de Investigaciones Biomédicas en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 28049 Madrid, Spain [2] Departamento de Biología Celular, Universidad de Valencia, 46100 Valencia, Spain.
authors: Martina
authors: M
authors: Kirstein
authors: 1] Centro de Investigaciones Biomédicas en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 28049 Madrid, Spain [2] Departamento de Biología Celular, Universidad de Valencia, 46100 Valencia, Spain.
authors: Isabel
authors: I
authors: Fariñas
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D049109:Cell Proliferation; D002478:Cells, Cultured; D007150:Immunohistochemistry; D053504:Matrix Metalloproteinases, Membrane-Associated / Q000378:metabolism*; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000201:enzymology*; D010446:Peptide Fragments / Q000378:metabolism
chemical_list: D015820:Cadherins; D010446:Peptide Fragments; D053504:Matrix Metalloproteinases, Membrane-Associated; C118502:Mmp24 protein, mouse