1. Academic Validation
  2. A SNX10/V-ATPase pathway regulates ciliogenesis in vitro and in vivo

A SNX10/V-ATPase pathway regulates ciliogenesis in vitro and in vivo

  • Cell Res. 2012 Feb;22(2):333-45. doi: 10.1038/cr.2011.134.
Yanqun Chen 1 Bin Wu Liangliang Xu Huapeng Li Jianhong Xia Wenguang Yin Zhuo Li Dawei Shi Song Li Shuo Lin Xiaodong Shu Duanqing Pei
Affiliations

Affiliation

  • 1 CAS 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, Guangdong 510530, China.
Abstract

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.

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