Clathrin and phosphatidylinositol-4,5-bisphosphate regulate autophagic lysosome reformation

被引：251

作者：

Rong, Yueguang ^{[1
]}

Liu, Mei ^{[1
]}

Ma, Liang ^{[1
]}

Du, Wanqing ^{[1
]}

Zhang, Hanshuo ^{[2
]}

Tian, Yuan ^{[3
]}

Cao, Zhen ^{[1
]}

Li, Ying ^{[4
]}

Ren, He ^{[5
]}

Zhang, Chuanmao ^{[5
]}

Li, Lin ^{[6
]}

Chen, She ^{[6
]}

Xi, Jianzhong ^{[2
]}

Yu, Li ^{[1
]}

机构：

[1] Tsinghua Univ, State Key Lab Biomembrane & Membrane Biotechnol, Peking Univ, Ctr Life Sci,Sch Life Sci, Beijing 100084, Peoples R China

[2] Peking Univ, Coll Engn, Beijing 100871, Peoples R China

[3] China Agr Univ, Coll Biol Sci, Beijing 100193, Peoples R China

[4] Tsinghua Univ, Cell Biol Core Facil, Beijing 100084, Peoples R China

[5] Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China

[6] Natl Inst Biol Sci, Prote Facil, Beijing 102206, Peoples R China

来源：

NATURE CELL BIOLOGY | 2012年 / 14卷 / 09期

基金：

美国国家科学基金会;

关键词：

MEDIATED ENDOCYTOSIS; TRANSPORT; PROTEINS; FAMILY; SITE;

D O I：

10.1038/ncb2557

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Autophagy is a lysosome-based degradation pathway. During autophagy, lysosomes fuse with autophagosomes to form autolysosomes. Following starvation-induced autophagy, nascent lysosomes are formed from autolysosomal membranes through an evolutionarily conserved cellular process, autophagic lysosome reformation (ALR), which is critical for maintaining lysosome homeostasis. Here we report that clathrin and phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P-2) regulate ALR. Combining a screen of candidates identified through proteomic analysis of purified ALR tubules, and large-scale RNAi knockdown, we unveiled a tightly regulated molecular pathway that controls lysosome homeostasis, in which clathrin and PtdIns(4,5)P-2 are the central components. Our functional study demonstrates the central role of clathrin and its associated proteins in cargo sorting, phospholipid conversion, initiation of autolysosome tubulation, and proto-lysosome budding during ALR. Our data not only uncover a molecular pathway by which lysosome homeostasis is maintained through the ALR process, but also reveal unexpected functions of clathrin and PtdIns(4,5)P-2 in lysosome homeostasis.

引用

页码：924 / +

页数：19

共 29 条

[1]

THE SEQUENCE OF PHOSPHATIDYLINOSITOL-4-PHOSPHATE 5-KINASE DEFINES A NOVEL FAMILY OF LIPID KINASES [J].