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ZFIN ID: ZDB-PUB-110817-6
A SNX10/V-ATPase pathway regulates ciliogenesis in vitro and in vivo
Chen, Y., Wu, B., Xu, L., Li, H., Xia, J., Yin, W., Li, Z., Li, S., Lin, S., Shu, X., and Pei, D.
Date: 2012
Source: Cell Research   22(2): 333-345 (Journal)
Registered Authors: Lin, Shuo, Pei, Desheng, Shu, Xiaodong
Keywords: none
MeSH Terms:
  • Animals
  • Body Patterning
  • Cell Line, Tumor
  • Centrosome/physiology
  • Cilia/physiology
  • Embryonic Development
  • Humans
  • Morphogenesis
  • Protein Binding
  • RNA Interference
  • RNA, Small Interfering/metabolism
  • Sorting Nexins/antagonists & inhibitors
  • Sorting Nexins/genetics
  • Sorting Nexins/metabolism*
  • Vacuolar Proton-Translocating ATPases/antagonists & inhibitors
  • Vacuolar Proton-Translocating ATPases/genetics
  • Vacuolar Proton-Translocating ATPases/metabolism*
  • Vacuoles/metabolism
  • Vacuoles/physiology
  • Zebrafish
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • rab GTP-Binding Proteins/metabolism
PubMed: 21844891 Full text @ Cell Res.
FIGURES
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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