RRC ID 53454
Author Liu K, Jian Y, Sun X, Yang C, Gao Z, Zhang Z, Liu X, Li Y, Xu J, Jing Y, Mitani S, He S, Yang C.
Title Negative regulation of phosphatidylinositol 3-phosphate levels in early-to-late endosome conversion.
Journal J Cell Biol
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.
Volume 212(2)
Pages 181-98
Published 2016-1-18
DOI 10.1083/jcb.201506081
PII jcb.201506081
PMID 26783301
PMC PMC4738380
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / metabolism* Carrier Proteins / metabolism* Endosomes / metabolism* Membrane Fusion Mutation Nerve Tissue Proteins / metabolism Phosphatidylinositol Phosphates / metabolism* Vesicular Transport Proteins / metabolism rab GTP-Binding Proteins / metabolism
IF 8.811
Times Cited 21
C.elegans tm3855 tm5210 tm5202 tm1125 tm2241 tm4475 tm327 tm2253 tm3171