Negative regulation of phosphatidylinositol 3-phosphate levels in early-to-late endosome conversion

The Journal of Cell Biology
Kai LiuChonglin Yang

Abstract

Phosphatidylinositol 3-phosphate (PtdIns3P) plays a central role in endosome fusion, recycling, sorting, and early-to-late endosome conversion, but the mechanisms that determine how the correct endosomal PtdIns3P level is achieved remain largely elusive. Here we identify two new factors, SORF-1 and SORF-2, as essential PtdIns3P regulators in Caenorhabditis elegans. Loss of sorf-1 or sorf-2 leads to greatly elevated endosomal PtdIns3P, which drives excessive fusion of early endosomes. sorf-1 and sorf-2 function coordinately with Rab switching genes to inhibit synthesis of PtdIns3P, allowing its turnover for endosome conversion. SORF-1 and SORF-2 act in a complex with BEC-1/Beclin1, and their loss causes elevated activity of the phosphatidylinositol 3-kinase (PI3K) complex. In mammalian cells, inactivation of WDR91 and WDR81, the homologs of SORF-1 and SORF-2, induces Beclin1-dependent enlargement of PtdIns3P-enriched endosomes and defective degradation of epidermal growth factor receptor. WDR91 and WDR81 interact with Beclin1 and inhibit PI3K complex activity. These findings reveal a conserved mechanism that controls appropriate PtdIns3P levels in early-to-late endosome conversion.

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Citations

Apr 4, 2017·Traffic·Chonglin Yang, Xiaochen Wang
Jul 18, 2018·The Journal of Biological Chemistry·Xinli MaHuanhuan Liang
Sep 21, 2017·The Journal of Cell Biology·James E Casanova, Bettina Winckler
Sep 2, 2017·The Journal of Cell Biology·Kai LiuChonglin Yang
Aug 28, 2019·Nature Chemical Biology·C Kimberly TsuiMichael C Bassik
Oct 13, 2016·Annual Review of Pharmacology and Toxicology·Shawn M Davidson, Matthew G Vander Heiden
Aug 28, 2020·Frontiers in Cell and Developmental Biology·Gregory M I RedpathJérémie Rossy
Apr 14, 2017·The Journal of Cell Biology·Xuezhao LiuChonglin Yang
Feb 13, 2021·Nature Communications·Yunkai ZhuRong Zhang
May 7, 2021·Journal of Molecular Neuroscience : MN·Amin Tadayoni NiaMorteza Oladnabi
May 6, 2021·The Journal of Cell Biology·Chonglin Yang, Xiaochen Wang

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Methods Mentioned

BETA
GTPases
nucleotide exchange
GTPase
pull-down
coIP
transfection
Co-IP
PCR
transgenic
confocal microscopy

Software Mentioned

Prism
softWoRx
Axiovision
DV Elite
FV10
ASW
DeltaVision
GraphPad
Excel

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