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

Frances C. Tilley, Matthew Gallon, Chong Luo, Chris M. Danson, Jing Zhou, Peter J. Cullen*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

3 Citations (Scopus)

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 atypicalG-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 endolysosomal 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.

Original languageEnglish
Article numberjcs211342
JournalJournal of Cell Science
Volume131
Issue number11
DOIs
Publication statusPublished - 1 Jun 2018

Keywords

  • Endosome
  • Polycystin-2
  • Retromer

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