Extracellular Signal-regulated Kinase 5 (ERK5) Mediates Prolactin-stimulated Adult Neurogenesis in the Subventricular Zone and Olfactory Bulb

Autor: Glen M. Abel, Zhengui Xia, Yung Wei Pan, Chay T. Kuo, Junhui Zou, Wenbin Wang, Tomasz Wietecha
Rok vydání: 2013
Předmět:
Zdroj: Journal of Biological Chemistry. 288:2623-2631
ISSN: 0021-9258
DOI: 10.1074/jbc.m112.401091
Popis: Prolactin-stimulated adult neurogenesis in the subventricular zone (SVZ) and olfactory bulb (OB) mediates several reproductive behaviors including mating/pregnancy, dominant male pheromone preference in females, and paternal recognition of offspring. However, downstream signaling mechanisms underlying prolactin-induced adult neurogenesis are completely unknown. We report here for the first time that prolactin activates extracellular signal-regulated kinase 5 (ERK5), a MAP kinase that is specifically expressed in the neurogenic regions of the adult mouse brain. Knockdown of ERK5 by retroviral infection of shRNA attenuates prolactin-stimulated neurogenesis in SVZ-derived adult neural stem/progenitor cells (aNPCs). Inducible erk5 deletion in adult neural stem cells of transgenic mice inhibits neurogenesis in the SVZ and OB following prolactin infusion or mating/pregnancy. These results identify ERK5 as a novel and critical signaling mechanism underlying prolactin-induced adult neurogenesis. Background: Signaling mechanisms underlying prolactin-induced adult neurogenesis are unknown. Results: Prolactin activates ERK5 in SVZ; suppression of ERK5 expression in vitro and erk5 deletion in vivo attenuates prolactin-induced adult neurogenesis. Conclusion: ERK5 is an important mediator in prolactin-stimulated adult neurogenesis. Significance: Elucidation of signaling pathways underlying prolactin-induced adult neurogenesis is critical for understanding the fundamental role of adult neurogenesis in reproductive functions and behaviors.
Databáze: OpenAIRE
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