Volume 17, No 11, Nov 2007
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 17 Issue 11, November 2007: 919-932
ORIGINAL ARTICLES
rSac3, a novel Sac domain phosphoinositide phosphatase, promotes neurite outgrowth in PC12 cells
Yiyuan Yuan1, Xiang Gao1, Ning Guo2,4, Hui Zhang3, Zhiqin Xie1, Meilei Jin2, Baoming Li3, Lei Yu4 and Naihe Jing1
1Laboratory of Molecular Cell Biology and Key Laboratory of Stem Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue yang Road, Shanghai 200031, China;
2Research Center of Biotechnology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 500 Cao bao Road, Shanghai 200233, China;
3Laboratory of Higher Brain Functions, Institute of Neurobiology, Institutes of Brain Science, Fudan University, 138 Yi xue yuan Road, Shanghai 200032, China;
4Department of Genetics and Center of Alcohol Studies, Rutgers University, 145 Bevier Road, Piscataway, NJ 08854, USA
Correspondence: Meilei Jin, Baoming Li, Lei Yu, Naihe Jing(njing@sibs.ac.cn)
Sac domain-containing proteins belong to a newly identified family of phosphoinositide phosphatases (the PIPPase family). Despite well-characterized enzymatic activity, the biological functions of this mammalian Sac domain PIPPase family remain largely unknown. We identified a novel Sac domain-containing protein, rat Sac3 (rSac3), which is widely expressed in various tissues and localized to the endoplasmic reticulum, Golgi complex and recycling endosomes. rSac3 displays PIPPase activity with PI(3)P, PI(4)P and PI(3,5)P2 as substrates in vitro, and a mutation in the catalytic core of the Sac domain abolishes its enzymatic activity. The expression of rSac3 is upregulated during nerve growth factor (NGF)-stimulated PC12 cell neuronal differentiation, and overexpression of this protein promotes neurite outgrowth in PC12 cells. Conversely, inhibition of rSac3 expression by antisense oligonucleotides reduces neurite outgrowth of NGF-stimulated PC12 cells, and the active site mutation of rSac3 eliminates its neurite-outgrowth-promoting activity. These results indicate that rSac3 promotes neurite outgrowth in differentiating neurons through its PIPPase activity, suggesting that Sac domain PIPPase proteins may participate in forward membrane trafficking from the endoplasmic reticulum and Golgi complex to the plasma membrane, and may function as regulators of this crucial process of neuronal cell growth and differentiation.
Cell Research (2007) 17:919-932. doi: 10.1038/cr.2007.82; published online 1 October 2007
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