RRC ID 59379
著者 McGough IJ, de Groot REA, Jellett AP, Betist MC, Varandas KC, Danson CM, Heesom KJ, Korswagen HC, Cullen PJ.
タイトル SNX3-retromer requires an evolutionary conserved MON2:DOPEY2:ATP9A complex to mediate Wntless sorting and Wnt secretion.
ジャーナル 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.
巻・号 9(1)
ページ 3737
公開日 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
引用数 11
リソース情報
線虫 tm1320 tm5356