Retromer associates with the cytoplasmic amino-terminus of polycystin-2.

Abstract:

:Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic human disease, with around 12.5 million people affected worldwide. ADPKD results from mutations in either PKD1 or PKD2, which encode the atypical G-protein coupled receptor polycystin-1 (PC1) and the transient receptor potential channel polycystin-2 (PC2), respectively. Although altered intracellular trafficking of PC1 and PC2 is an underlying feature of ADPKD, the mechanisms which govern vesicular transport of the polycystins through the biosynthetic and endosomal membrane networks remain to be fully elucidated. Here, we describe an interaction between PC2 and retromer, a master controller for the sorting of integral membrane proteins through the endo-lysosomal network. We show that association of PC2 with retromer occurs via a region in the PC2 cytoplasmic amino-terminal domain, independently of the retromer-binding Wiskott-Aldrich syndrome and scar homologue (WASH) complex. Based on observations that retromer preferentially interacts with a trafficking population of PC2, and that ciliary levels of PC1 are reduced upon mutation of key residues required for retromer association in PC2, our data are consistent with the identification of PC2 as a retromer cargo protein.This article has an associated First Person interview with the first author of the paper.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

Tilley FC,Gallon M,Luo C,Danson CM,Zhou J,Cullen PJ

doi

10.1242/jcs.211342

subject

Has Abstract

pub_date

2018-06-06 00:00:00

issue

11

eissn

0021-9533

issn

1477-9137

pii

jcs.211342

journal_volume

131

pub_type

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