Interdependent assembly of specific regulatory lipids and membrane fusion proteins into the vertex ring domain of docked vacuoles

被引:170
作者
Fratti, RA [1 ]
Jun, YS [1 ]
Metz, AJ [1 ]
Margolis, N [1 ]
Wickner, W [1 ]
机构
[1] Dartmouth Coll Sch Med, Dept Biochem, Hanover, NH 03755 USA
关键词
D O I
10.1083/jcb.200409068
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Membrane microdomains are assembled by lipid partitioning (e.g., rafts) or by protein-protein interactions (e.g., coated vesicles). During docking, yeast vacuoles assemble "vertex" ring-shaped microdomains around the periphery of their apposed membranes. Vertices are selectively enriched in the Rab GTPase Ypt7p, the homotypic fusion and vacuole protein sorting complex (HOPS)-VpsC Rab effector complex, SNAREs, and actin. Membrane fusion initiates at vertex microdomains. We now find that the "regulatory lipids" ergosterol, diacylglycerol and 3- and 4-phosphoinositides accumulate at vertices in a mutually interdependent manner. Regulatory lipids are also required for the vertex enrichment of SNAREs, Ypt7p, and HOPS. Conversely, SNAREs and actin regulate phosphatidylinositol 3-phosphate vertex enrichment. Though the PX domain of the SNARE Vam7p has direct affinity for only 3-phosphoinositides, all the regulatory lipids which are needed for vertex assembly affect Vam7p association with vacuoles. Thus, the assembly of the vacuole vertex ring micro-domain arises from interdependent lipid and protein partitioning and binding rather than either lipid partitioning or protein interactions alone.
引用
收藏
页码:1087 / 1098
页数:12
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