A feed-forward mechanism involving the NOX complex and RyR-mediated ca2 + release during axonal specification

Physiological levels of ROS support neurite outgrowth and axonal specification, but the mechanisms by which ROS are able to shape neurons remain unknown. Ca2 +, a broad intracellular second messenger, promotes both Rac1 activation and neurite extension. Ca2 + release from the endoplasmic reticulum,...

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Detalles Bibliográficos
Autores: Wilson Rodriguez, Carlos, Munoz-Palma, Ernesto, Henriquez, Daniel R., Palmisano, Ilaria, Nuñez, Marco Tulio, Di Giovanni, Simone, González Billault, Christian
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/72755
Acceso en línea:http://hdl.handle.net/11336/72755
Access Level:acceso abierto
Palabra clave:ACTIN CYTOSKELETON
AXON DEVELOPMENT
CALCIUM SIGNALING
NADPH OXIDASE
NEURONAL DIFFERENTIATION
REACTIVE OXYGEN SPECIES
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
Descripción
Sumario:Physiological levels of ROS support neurite outgrowth and axonal specification, but the mechanisms by which ROS are able to shape neurons remain unknown. Ca2 +, a broad intracellular second messenger, promotes both Rac1 activation and neurite extension. Ca2 + release from the endoplasmic reticulum, mediated by both the IP3R1 and ryanodine receptor (RyR) channels, requires physiological ROS levels that are mainly sustained by the NADPH oxidase (NOX) complex. In this work, we explore the contribution of the link between NOX and RyR-mediated Ca2 + release toward axonal specification of rat hippocampal neurons. Using genetic approaches, we find thatNOXactivation promotes both axonal development and Rac1 activation through a RyR-mediated mechanism, which in turn activates NOX through Rac1, one of the NOX subunits. Collectively, these data suggest a feedforward mechanism that integrates both NOX activity and RyR-mediated Ca2 + release to support cellular mechanisms involved in axon development.