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
|
PII |
PGENETICS-D-21-00051
|
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
|
Resource |
C.elegans |
tm1595
tm5356
tm847
tm2423
tm2404
tm3643
tm1320 |