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 |
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| Rok vydání: | 2013 |
| Předmět: |
endocrine system
Cell signaling medicine.medical_specialty Genotype Neurogenesis Subventricular zone Biology Biochemistry Mice Internal medicine STAT5 Transcription Factor medicine Animals Molecular Biology Mitogen-Activated Protein Kinase 7 Mice Knockout Brain Mapping Microscopy Confocal Brain Cell Biology Olfactory Bulb Recombinant Proteins Neural stem cell Prolactin Cell biology Olfactory bulb Tamoxifen Neuropoiesis Endocrinology medicine.anatomical_structure Female Signal transduction Gene Deletion hormones hormone substitutes and hormone antagonists Signal Transduction |
| 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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