Early But Not Delayed Optogenetic RAF Activation Promotes Astrocytogenesis in Mouse Neural Progenitors

JOURNAL OF MOLECULAR BIOLOGY

卷:432

Article

Su, Yixun¹  Huang, Xiaomin¹  Huang, Zhangsen¹  Huang, Taida¹  Li, Tao²  Fan, Huaxun³  Zhang, Kai³  Yi, Chenju¹ 

[1] Sun Yat Sen Univ, Affiliated Hosp 7, Shenzhen 518107, Peoples R China

[2] Army Med Univ, Third Mil Med Univ, Chongqing Key Lab Neurobiol, Dept Histol & Embryol, Chongqing 400038, Peoples R China

[3] Univ Illinois, Sch Mol & Cellular Biol, Dept Biochem, Urbana, IL 61801 USA

关键词: RAF1;    Optogenetic;    OptoRAF1;    neural progenitor;    astrocytogenesis;   

DOI  :  10.1016/j.jmb.2020.06.020

来源: Elsevier

【 摘 要 】

The RAS/RAF/MEK/ERK pathway promotes gliogenesis but the kinetic role of RAF1, a key RAF kinase, in the induction of astrocytogenesis remains to be elucidated. To address this challenge, we determine the temporal functional outcome of RAF1 during mouse neural progenitor cell differentiation using an optogenetic RAF1 system (OptoRAF1). OptoRAF1 allows for reversible activation of the RAF/MEK/ERK pathway via plasma membrane recruitment of RAF1 based on blue light-sensitive protein dimerizer CRY2/CIB1. We found that early light-induced OptoRAF1 activation in neural progenitor cells promotes cell proliferation and increased expression of glial markers and glia-enriched genes. However, delayed OptoRAF1 activation in differentiated neural progenitor had little effect on glia marker expression, suggesting that RAF1 is required to promote astrocytogenesis only within a short time window. In addition, activation of OptoRAF1 did not have a significant effect on neurogenesis, but was able to promote neuronal neurite growth. (C) 2020 The Authors. Published by Elsevier Ltd.

【 授权许可】

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