Autocrine vitamine K-dependent proteins regulate neural stem cells proliferation

Abstract

Event Abstract Back to Event Autocrine vitamine K-dependent proteins regulate neural stem cells proliferation Valerie Coronas1* 1 Universite de Poitiers, UMR 6187 CNRS, France The adult mammalian brain hosts neural stem cells (NSC) within the subventricular zone (SVZ). Although many studies have identified exogenous mechanisms of NSC control, the endogenous mechanisms regulating the neurogenic activity of NSC have only poorly been explored. Vitamin K-dependent proteins (VKDP) are a family of secreted proteins in which some glutamyl residues are post-translationally modified to γ-carboxyglutamic acid residues. This enzymatic reaction requires vitamin K and is necessary for the secretion and/or activity of vitamin K-dependent proteins. Warfarin, a widely used anticoagulant, antagonizes vitamin K and thereby blocks functional VKDP production. Mainly known for their role in coagulation, vitamin K-dependent proteins have recently been shown to regulate proliferation and differentiation on various cell types. In the present study, we investigated both in vitro and in vivo possible involvement of vitamin K-dependent proteins in the regulation of NSC proliferation and differentiation. Blockade of functional vitamin K-dependent proteins production, using the anti-coagulant warfarin, promoted SVZ cells proliferation in vitro and in vivo. Mechanisms underlying warfarin effects were next analyzed in vitro. Vitamin K as well as VKDP released by SVZ cells in conditioned media reversed warfarin effects, suggesting that secreted endogenous VKDP restrain SVZ cells proliferation. RT-PCR, Western blot and immunochemistry analyses revealed that neural stem cells express two secreted VKDP, protein-S and Gas 6, and their receptors Axl, Tyro-3 and Mer. Exogenous Gas-6 addition affected neither basal nor warfarin promoted growth of SVZ cells. Conversely, protein-S inhibited SVZ cell proliferation and reversed warfarin growth promoting activity. Our study identifies vitamin K-dependent proteins as major actors in the control of the SVZ neurogenesis and opens new insights in the regulation of stem cells activity by vascular determinants. Keywords: coagulation control, proliferation Conference: 3rd Mediterranean Conference of Neuroscience , Alexandria, Egypt, 13 Dec - 16 Dec, 2009. Presentation Type: Oral Presentation Topic: Symposium 13 – Physiological involvement of neurogenic niches: from stem cells to clinics Citation: Coronas V (2009). Autocrine vitamine K-dependent proteins regulate neural stem cells proliferation. Front. Neurosci. Conference Abstract: 3rd Mediterranean Conference of Neuroscience . doi: 10.3389/conf.neuro.01.2009.16.059 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 19 Nov 2009; Published Online: 19 Nov 2009. * Correspondence: Valerie Coronas, Universite de Poitiers, UMR 6187 CNRS, 86022 Poitiers, France, valerie.coronas@univ-poitiers.fr Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Valerie Coronas Google Valerie Coronas Google Scholar Valerie Coronas PubMed Valerie Coronas Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.