Parp3 Promotes Astrocytic Differentiation Through a Tight Regulation of Nox4-induced ROS and MTorc2 Activation

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2020 Nov 7

PMID 33159039

Citations 10

Authors

Jose-Manuel Rodriguez-Vargas

Kathline Martin-Hernandez

Wei Wang

Nicolas Kunath

Rajikala Suganthan

Jean-Christophe Ame

F Javier Oliver

Jing Ye

Magnar Bjoras

Francoise Dantzer

Affiliations

Soon will be listed here.

Abstract

Parp3 is a member of the Poly(ADP-ribose) polymerase (Parp) family that has been characterized for its functions in strand break repair, chromosomal rearrangements, mitotic segregation and tumor aggressiveness. Yet its physiological implications remain unknown. Here we report a central function of Parp3 in the regulation of redox homeostasis in continuous neurogenesis in mice. We show that the absence of Parp3 provokes Nox4-induced oxidative stress and defective mTorc2 activation leading to inefficient differentiation of post-natal neural stem/progenitor cells to astrocytes. The accumulation of ROS contributes to the decreased activity of mTorc2 as a result of an oxidation-induced and Fbxw7-mediated ubiquitination and degradation of Rictor. In vivo, mTorc2 signaling is compromised in the striatum of naïve post-natal Parp3-deficient mice and 6 h after acute hypoxia-ischemia. These findings reveal a physiological function of Parp3 in the tight regulation of striatal oxidative stress and mTorc2 during astrocytic differentiation and in the acute phase of hypoxia-ischemia.

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