GOLPH3: a Golgi phosphatidylinositol(4)phosphate effector that directs vesicle trafficking and drives cancer

被引：68
作者：
Kuna, Ramya S. [1 ]
Field, Seth J. [1 ]
机构：
[1] Univ Calif San Diego, Dept Med, Div Endocrinol & Metab, La Jolla, CA 92093 USA
来源：
JOURNAL OF LIPID RESEARCH | 2019年 / 60卷 / 02期
基金：
美国国家卫生研究院;
关键词：
lipids; phosphoinositides; phospholipids/trafficking; cell signaling; Golgi apparatus; myosin; 18A; POTENTIAL THERAPEUTIC TARGET; CELL LUNG-CANCER; SIGNALING PATHWAY; POOR-PROGNOSIS; BREAST-CANCER; DNA-DAMAGE; RAPAMYCIN SENSITIVITY; HIGH EXPRESSION; GLIOMA-CELLS; PROTEIN;
D O I：
10.1194/jlr.R088328
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
GOLPH3 is a peripheral membrane protein localized to the Golgi and its vesicles, but its purpose had been unclear. We found that GOLPH3 binds specifically to the phosphoinositide phosphatidylinositol(4)phosphate [PtdIns(4)P], which functions at the Golgi to promote vesicle exit for trafficking to the plasma membrane. PtdIns(4)P is enriched at the trans-Golgi and so recruits GOLPH3. Here, a GOLPH3 complex is formed when it binds to myosin18A (MYO18A), which binds F-actin. This complex generates a pulling force to extract vesicles from the Golgi; interference with this GOLPH3 complex results in dramatically reduced vesicle trafficking. The GOLPH3 complex has been identified as a driver of cancer in humans, likely through multiple mechanisms that activate secretory trafficking. In this review, we summarize the literature that identifies the nature of the GOLPH3 complex and its role in cancer. We also consider the GOLPH3 complex as a hub with the potential to reveal regulation of the Golgi and suggest the possibility of GOLPH3 complex inhibition as a therapeutic approach in cancer.
引用
收藏
页码：269 / 275
页数：7
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