VPS26A and VPS26B subunits define distinct Retromer complexes

Bugarcic, Andrea, Yang, Zhe, Kerr, Markus C., Griffith, John Griffin, Collins, Brett M. and Teasdale, Rohan D. (2011) VPS26A and VPS26B subunits define distinct Retromer complexes. Traffic, 12 12: 1759-1773. doi:10.1111/j.1600-0854.2011.01284.x

Author Bugarcic, Andrea
Yang, Zhe
Kerr, Markus C.
Griffith, John Griffin
Collins, Brett M.
Teasdale, Rohan D.
Title VPS26A and VPS26B subunits define distinct Retromer complexes
Journal name Traffic   Check publisher's open access policy
ISSN 1600-0854
Publication date 2011-12
Sub-type Article (original research)
DOI 10.1111/j.1600-0854.2011.01284.x
Volume 12
Issue 12
Start page 1759
End page 1773
Total pages 15
Place of publication Malden, MA, United States
Publisher Wiley-Blackwell Publishing
Collection year 2012
Language eng
Formatted abstract
The trimeric Vps29-Vps35-Vps26 sub-complex of Retromer mediates retrograde transport of transmembrane proteins from endosomes to the TGN. Our group has recently identified a Vps26 paralogue, Vps26B, which is able to suppress the expression of Vps26A when exogenously expressed in mammalian cells and defines a distinct Retromer complex (Vps26B-Retromer) in vivo and in vitro. In the present study, we use HEK293 cells stably expressing either Vps26A-myc or Vps26B-myc to address the role of Retromer cargo transport and subcellular localization of the two core Retromer complexes as defined by the two mammalian-specific Vps26 paralogs. Vps26B-Retromer, like Vps26A-Retromer, associates with TBC1D5 and GOLPH3. In contrast, no interaction between Vps26B-Retromer and CI-M6PR was detected, leading to degradation of this receptor and an increase in cathepsin D secretion. Colocalisation of Vps26 paralogues with different endosomally located Rab proteins shows prolonged association of Vps26B-Retromer with maturing endosomes relative to Vps26A-Retromer. Interestingly, the cycling of CI-M6PR is restored upon deletion of the variable Vps26B C-terminal region indicating this region is directly responsible for the differential function of the two paralogues. In summary, we show that the two distinct Retromer complexes defined by different Vps26 paralogues are not functionally equivalent and that the Vps26B C-terminal region can control cargo selection of the Vps26B-Retromer.
Keyword Endosome
Protein trafficking
Cation-Independent mannose 6-phospate receptor (CI-M6PR)
Trans-Golgi network (TGN)
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes "Accepted Article" 15 September 2011 (Accepted, unedited articles published online for future issues), published online 17 October 2011

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Biomedical Sciences Publications
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 26 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 20 Sep 2011, 12:31:54 EST by Brett Collins on behalf of School of Biomedical Sciences