Rab-Effector-Kinase Interplay Modulates Intralumenal Fragment Formation during Vacuole Fusion
Rab-Effector-Kinase Interplay Modulates Intralumenal Fragment Formation during Vacuole Fusion
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DOI：
10.1016/j.devcel.2018.09.002
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发表时间：
2018-10-08
影响因子：
11.8
通讯作者：
Brett，Christopher Leonard
中科院分区：
文献类型：
--
作者：
Karim，Mahmoud Abdul;McNally，Erin Kate;Brett，Christopher Leonard
在酿酒酵母中，当液泡溶酶体（或液泡）融合时，一部分膜被内化和分解代谢。这种腔内片段（ILF）的形成对于细胞器蛋白质和脂质的稳态和重塑是重要的。但是，ILF的形成是如何优化膜周转还不清楚。在这里，我们表明，较少的ILF形成时，Rab-GTpt 7和它的效应Vps 41（系链复合物HOPS的亚基）之间的相互作用被点突变（Ypt 7-D44 N）中断。随后通过酪蛋白激酶Yck 3磷酸化Vps 41阻止脂质双层孔形成所需的trans-SNARE复合物的稳定化。损害ILF形成阻止从液泡膜清除错误折叠的蛋白质，并促进细胞器渗透性和细胞死亡。我们建议HOPS协调Rab，激酶和SNARE循环，以调节ILF的大小在液泡融合，调节脂质和蛋白质的营业额重要的质量控制和膜的完整性。
Upon vacuolar lysosome (or vacuole) fusion inS. cerevisiae, a portion of membrane is internalized and catabolized. Formation of this intralumenal fragment (ILF) is important for organelle protein and lipid homeostasis and remodeling. But how ILF formation is optimized for membrane turnover is not understood. Here, we show that fewer ILFs form when the interaction between the Rab-GTPase Ypt7 and its effector Vps41 (a subunit of the tethering complex HOPS) is interrupted by a point mutation (Ypt7-D44N). Subsequent phosphorylation of Vps41 by the casein kinase Yck3 prevents stabilization of trans-SNARE complexes needed for lipid bilayer pore formation. Impairing ILF formation prevents clearance of misfolded proteins from vacuole membranes and promotes organelle permeability and cell death. We propose that HOPS coordinates Rab, kinase, and SNARE cycles to modulate ILF size during vacuole fusion, regulating lipid and protein turnover important for quality control and membrane integrity.