Volume 22, No 2, Feb 2012
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 22 Issue 2, February 2012: 333-345
ORIGINAL ARTICLES
A SNX10/V-ATPase pathway regulates ciliogenesis in vitro and in vivo
Yanqun Chen1,2,*, Bin Wu1,2,*, Liangliang Xu1, Huapeng Li1, Jianhong Xia1, Wenguang Yin1, Zhuo Li1, Song Li3, Shuo Lin3, Xiaodong Shu1 and D
1CAS Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
2School of Life Sciences, University of Science and Technology of China, Hefei 230027, China
3Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School of Peking University, Shenzhen 518055, China
Correspondence: Xiaodong Shu, Duanqing Pei,(shu_xiaodong@gibh.ac.cn pei_duanqing@gibh.ac.cn)
Sorting nexins (SNXs) are phosphoinositide-binding proteins implicated in the sorting of various membrane proteins
in vitro, but the
in vivo functions of them remain largely unknown. We reported previously that SNX10 is a unique member of the SNX family genes in that it has vacuolation activity in cells. We investigate the biological function of SNX10 by loss-of-function assay in this study and demonstrate that SNX10 is required for the formation of primary cilia in cultured cells. In zebrafish, SNX10 is involved in ciliogenesis in the Kupffer's vesicle and essential for left-right patterning of visceral organs. Mechanistically, SNX10 interacts with V-ATPase complex and targets it to the centrosome where ciliogenesis is initiated. Like SNX10, V-ATPase regulates ciliogenesis
in vitro and
in vivo and does so synergistically with SNX10. We further discover that SNX10 and V-ATPase regulate the ciliary trafficking of Rab8a, which is a critical regulator of ciliary membrane extension. These results identify an SNX10/V-ATPase-regulated vesicular trafficking pathway that is crucial for ciliogenesis, and reveal that SNX10/V-ATPase, through the regulation of cilia formation in various organs, play an essential role during early embryonic development.
Cell Research (2012) 22:333-345. doi:10.1038/cr.2011.134; published online 16 August 2011
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