| RRC ID |
59379
|
| Author |
McGough IJ, de Groot REA, Jellett AP, Betist MC, Varandas KC, Danson CM, Heesom KJ, Korswagen HC, Cullen PJ.
|
| Title |
SNX3-retromer requires an evolutionary conserved MON2:DOPEY2:ATP9A complex to mediate Wntless sorting and Wnt secretion.
|
| Journal |
Nat Commun
|
| Abstract |
Wntless transports Wnt morphogens to the cell surface and is required for Wnt secretion and morphogenic gradients formation. Recycling of endocytosed Wntless requires the sorting nexin-3 (SNX3)-retromer-dependent endosome-to-Golgi transport pathway. Here we demonstrate the essential role of SNX3-retromer assembly for Wntless transport and report that SNX3 associates with an evolutionary conserved endosome-associated membrane re-modelling complex composed of MON2, DOPEY2 and the putative aminophospholipid translocase, ATP9A. In vivo suppression of Ce-mon-2, Ce-pad-1 or Ce-tat-5 (respective MON2, DOPEY2 and ATP9A orthologues) phenocopy a loss of SNX3-retromer function, leading to enhanced lysosomal degradation of Wntless and a Wnt phenotype. Perturbed Wnt signalling is also observed upon overexpression of an ATPase-inhibited TAT-5(E246Q) mutant, suggesting a role for phospholipid flippase activity during SNX3-retromer-mediated Wntless sorting. Together, these findings provide in vitro and in vivo mechanistic details to describe SNX3-retromer-mediated transport during Wnt secretion and the formation of Wnt-morphogenic gradients.
|
| Volume |
9(1)
|
| Pages |
3737
|
| Published |
2018-9-13
|
| DOI |
10.1038/s41467-018-06114-3
|
| PII |
10.1038/s41467-018-06114-3
|
| PMID |
30213940
|
| PMC |
PMC6137200
|
| MeSH |
Adenosine Triphosphatases / metabolism*
Animals
Biological Transport
Caenorhabditis elegans
Endosomes / metabolism*
Golgi Apparatus / metabolism*
Green Fluorescent Proteins / metabolism
HEK293 Cells
HeLa Cells
Humans
Membrane Transport Proteins / metabolism*
Mutation
Phenotype
Phospholipid Transfer Proteins / metabolism*
Protein Binding
Protein Domains
Proteomics
Proton-Translocating ATPases / metabolism*
RNA Interference
Sorting Nexins / metabolism*
Transgenes
Vesicular Transport Proteins / metabolism*
Wnt Proteins / metabolism*
|
| IF |
11.878
|
| Times Cited |
11
|
| Resource |
| C.elegans |
tm1320
tm5356 |
