细胞生物学
内体
生物
植物脂质转运蛋白
突变体
膜
磷酸酶
酵母
溶酶体
酿酒酵母
磷酸化
生物化学
化学
基因
酶
细胞内
标识
DOI:10.1101/2022.07.12.499833
摘要
ER tubules form and maintain membrane contact sites (MCSs) with late endosomes/lysosomes (LE/lys). The molecular composition and cellular functions of these MCSs are poorly understood. Here we find that Tex2, an SMP domain-containing lipid transfer protein conserved in metazoen and yeast, is a tubular ER protein, and enriches at ER- LE/lys MCSs dependent on TMEM55, phosphatases that convert PI(4,5)P2 to PI5P on LE/lys. We show that the Tex2-TMEM55 interaction occurs between a N-terminal region of Tex2 and a catalytic motif in PTase domain of TMEM55. The Tex2-TMEM55 interaction can be regulated by endosome-resident type 2 PI4K activities. Functionally, Tex2 knockout results in severe defects in lysosomal digestive capacity and blocked autophagic flow, as well as an aberrant accumulation of PI3P on the LE/lys membranes. These defects can be substantially rescued by wild type Tex2 other than a lipid transfer-defective Tex2 mutant, indicating an important role of lipid transfer in these processes. Together our data identify Tex2 as a tubular ER protein that resides at TMEM55-depedent ER-LE/lys MCSs required for lysosomal functions.
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