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Gsk3 beta-dzip1-rab8 cascade regulates ciliogenesis after mitosis
Zhang, Boyan1; Zhang, Tingting; Wang, Guopeng; Wang, Gang; Chi, Wangfei; Jiang, Qing; Zhang, Chuanmao
刊名Plos biology
2015-04-01
卷号13期号:4页码:25
ISSN号1545-7885
DOI10.1371/journal.pbio.1002129
通讯作者Zhang, boyan()
英文摘要The primary cilium, which disassembles before mitotic entry and reassembles after mitosis, organizes many signal transduction pathways that are crucial for cell life and individual development. however, how ciliogenesis is regulated during the cell cycle remains largely unknown. here we show that gsk3 beta, dzip1, and rab8 co-regulate ciliogenesis by promoting the assembly of the ciliary membrane after mitosis. immunofluorescence and super-resolution microscopy showed that dzip1 was localized to the periciliary diffusion barrier and enriched at the mother centriole. knockdown of dzip1 by short hairpin rnas led to failed ciliary localization of rab8, and rab8 accumulation at the basal body. dzip1 preferentially bound to rab8(gdp) and promoted its dissociation from its inhibitor gdi2 at the pericentriolar region, as demonstrated by sucrose gradient centrifugation of purified basal bodies, immunoprecipitation, and acceptor-bleaching fluorescence resonance energy transfer assays. by means of in vitro phosphorylation, in vivo gel shift, phospho-peptide identification by mass spectrometry, and gst pulldown assays, we demonstrated that dzip1 was phosphorylated by gsk3 beta at s520 in g0 phase, which increased its binding to gdi2 to promote the release of rab8(gdp) at the cilium base. moreover, ciliogenesis was inhibited by overexpression of the gsk3 beta-nonphosphorylatable dzip1 mutant or by disabling of gsk3 beta by specific inhibitors or knockout of gsk3 beta in cells. collectively, our data reveal a unique cascade consisting of gsk3 beta, dzip1, and rab8 that regulates ciliogenesis after mitosis.
WOS关键词PRIMARY CILIUM ; RAB PROTEINS ; NUCLEOTIDE-EXCHANGE ; TRANSPORT PROTEIN ; GDI DISPLACEMENT ; CILIARY MEMBRANE ; CELL-CYCLE ; COMPLEX ; PHOSPHORYLATION ; CENTROSOME
WOS研究方向Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics
WOS类目Biochemistry & Molecular Biology ; Biology
语种英语
出版者PUBLIC LIBRARY SCIENCE
WOS记录号WOS:000354824500022
内容类型期刊论文
URI标识http://www.corc.org.cn/handle/1471x/2376553
专题中国科学院大学
通讯作者Zhang, Boyan
作者单位1.Peking Univ, Key Lab Cell Proliferat & Differentiat, Minist Educ, Coll Life Sci, Beijing 100871, Peoples R China
2.Peking Univ, State Key Lab Biomembrane & Membrane Biotechnol, Coll Life Sci, Beijing 100871, Peoples R China
推荐引用方式
GB/T 7714
Zhang, Boyan,Zhang, Tingting,Wang, Guopeng,et al. Gsk3 beta-dzip1-rab8 cascade regulates ciliogenesis after mitosis[J]. Plos biology,2015,13(4):25.
APA Zhang, Boyan.,Zhang, Tingting.,Wang, Guopeng.,Wang, Gang.,Chi, Wangfei.,...&Zhang, Chuanmao.(2015).Gsk3 beta-dzip1-rab8 cascade regulates ciliogenesis after mitosis.Plos biology,13(4),25.
MLA Zhang, Boyan,et al."Gsk3 beta-dzip1-rab8 cascade regulates ciliogenesis after mitosis".Plos biology 13.4(2015):25.
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