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Nat Cell Biol. 2014 Jul;16(7):629-38. doi: 10.1038/ncb2993. Epub 2014 Jun 22.

MT5-MMP regulates adult neural stem cell functional quiescence through the cleavage of N-cadherin.

Author information

1
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.
2
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
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.
4
Cic BioGUNE, Parque Tecnológico de Vizcaya, 48160 Derio, Spain.
5
Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Oncología (IUOPA), Universidad de Oviedo, 33006 Oviedo, Spain.

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.

PMID:
24952463
DOI:
10.1038/ncb2993
[Indexed for MEDLINE]

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