title: SNX17 regulates Notch pathway and pancreas development through the retromer-dependent recycling of Jag1.
abstract: BACKGROUND
  Notch is one of the most important signaling pathways involved in cell fate determination. Activation of the Notch pathway requires the binding of a membrane-bound ligand to the Notch receptor in the adjacent cell which induces proteolytic cleavages and the activation of the receptor. A unique feature of the Notch signaling is that processes such as modification, endocytosis or recycling of the ligand have been reported to play critical roles during Notch signaling, however, the underlying molecular mechanism appears context-dependent and often controversial.
  
  
  RESULTS
  Here we identified SNX17 as a novel regulator of the Notch pathway. SNX17 is a sorting nexin family protein implicated in vesicular trafficking and we find it is specifically required in the ligand-expressing cells for Notch signaling. Mechanistically, SNX17 regulates the protein level of Jag1a on plasma membrane by binding to Jag1a and facilitating the retromer-dependent recycling of the ligand. In zebrafish, inhibition of this SNX17-mediated Notch signaling pathway results in defects in neurogenesis as well as pancreas development.
  
  
  CONCLUSIONS
  Our results reveal that SNX17, by acting as a cargo-specific adaptor, promotes the retromer dependent recycling of Jag1a and Notch signaling and this pathway is involved in cell fate determination during zebrafish neurogenesis and pancreas development.
authors.affiliation: 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.
authors.forename: Wenguang
authors.initials: W
authors.lastname: Yin
authors.affiliation: 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.
authors.forename: Dapeng
authors.initials: D
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Nian
authors.initials: N
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Liangliang
authors.initials: L
authors.lastname: Xu
authors.affiliation: Key Laboratory of Chemical Genomics, Shenzhen Graduate School of Peking University, Shenzhen, 518055 China.
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.affiliation: Key Laboratory of Chemical Genomics, Shenzhen Graduate School of Peking University, Shenzhen, 518055 China ; Department of Molecular, Cell & Developmental Biology, University of California, Los Angeles, CA USA.
authors.forename: Shuo
authors.initials: S
authors.lastname: Lin
authors.affiliation: 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.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Shu
authors.affiliation: 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.
authors.forename: Duanqing
authors.initials: D
authors.lastname: Pei