RRC ID 76073
Author Tian Y, Kang Q, Shi X, Wang Y, Zhang N, Ye H, Xu Q, Xu T, Zhang R.
Title SNX-3 mediates retromer-independent tubular endosomal recycling by opposing EEA-1-facilitated trafficking.
Journal PLoS Genet
Abstract Early endosomes are the sorting hub on the endocytic pathway, wherein sorting nexins (SNXs) play important roles for formation of the distinct membranous microdomains with different sorting functions. Tubular endosomes mediate the recycling of clathrin-independent endocytic (CIE) cargoes back toward the plasma membrane. However, the molecular mechanism underlying the tubule formation is still poorly understood. Here we screened the effect on the ARF-6-associated CIE recycling endosomal tubules for all the SNX members in Caenorhabditis elegans (C. elegans). We identified SNX-3 as an essential factor for generation of the recycling tubules. The loss of SNX-3 abolishes the interconnected tubules in the intestine of C. elegans. Consequently, the surface and total protein levels of the recycling CIE protein hTAC are strongly decreased. Unexpectedly, depletion of the retromer components VPS-26/-29/-35 has no similar effect, implying that the retromer trimer is dispensable in this process. We determined that hTAC is captured by the ESCRT complex and transported into the lysosome for rapid degradation in snx-3 mutants. Interestingly, EEA-1 is increasingly recruited on early endosomes and localized to the hTAC-containing structures in snx-3 mutant intestines. We also showed that SNX3 and EEA1 compete with each other for binding to phosphatidylinositol-3-phosphate enriching early endosomes in Hela cells. Our data demonstrate for the first time that PX domain-only C. elegans SNX-3 organizes the tubular endosomes for efficient recycling and retrieves the CIE cargo away from the maturing sorting endosomes by competing with EEA-1 for binding to the early endosomes. However, our results call into question how SNX-3 couples the cargo capture and membrane remodeling in the absence of the retromer trimer complex.
Volume 17(6)
Pages e1009607
Published 2021-6-1
DOI 10.1371/journal.pgen.1009607
PMID 34081703
PMC PMC8219167
MeSH ADP-Ribosylation Factor 6 ADP-Ribosylation Factors / genetics* ADP-Ribosylation Factors / metabolism Animals Biological Transport Caenorhabditis elegans / cytology Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Cell Membrane / metabolism Endosomal Sorting Complexes Required for Transport / genetics Endosomal Sorting Complexes Required for Transport / metabolism Endosomes / metabolism* Epithelial Cells / cytology Epithelial Cells / metabolism* Gene Expression Regulation HeLa Cells Humans Intestines / cytology Lysosomes / metabolism Phosphatidylinositol Phosphates / metabolism Protein Isoforms / genetics Protein Isoforms / metabolism Proteolysis Signal Transduction Sorting Nexins / deficiency Sorting Nexins / genetics* Vesicular Transport Proteins / genetics* Vesicular Transport Proteins / metabolism
C.elegans tm1595 tm5356 tm847 tm2423 tm2404 tm3643 tm1320