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Recruitment of the endosomal WASH complex is mediated by the extended ‘tail’ of Fam21 binding to the retromer protein Vps35
Abstract
The retromer complex is a conserved endosomal protein sorting complex that sorts membrane proteins into nascent endosomal tubules. The recognition of membrane proteins is mediated by the cargo-selective retromer complex, a stable trimer of the Vps35 (vacuolar protein sorting 35), Vps29 and Vps26 proteins. We have recently reported that the cargo-selective retromer complex associates with the WASH (Wiskott–Aldrich syndrome homologue) complex, a multimeric protein complex that regulates tubule dynamics at endosomes. In the present study, we show that the retromer–WASH complex interaction occurs through the long unstructured ‘tail’ domain of the WASH complex–Fam21 protein binding to Vps35, an interaction that is necessary and sufficient to target the WASH complex to endosomes. The Fam21-tail also binds to FKBP15 (FK506-binding protein 15), a protein associated with ulcerative colitis, to mediate the membrane association of FKBP15. Elevated Fam21-tail expression inhibits the association of the WASH complex with retromer, resulting in increased cytoplasmic WASH complex. Additionally, overexpression of the Fam21-tail results in cell-spreading defects, implicating the activity of the WASH complex in regulating the mobilization of membrane into the endosome-to-cell surface pathway.
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SNX27 regulates cargo recycling by engaging with the Retromer complex, a SNX-BAR dimer, and the WASH complex.
“SNX27 regulates cargo recycling by engaging with the Retromer complex (VPS35, VPS26A/B, and VPS29), a SNX–Bin/Amphiphysin/Rvs (BAR) dimer (SNX1/2 in complex with SNX5/6), and the WASH complex”
From PI(3)P coordinates SNX17- and SNX27-dependent protein recycling for long-term synaptic plasticity (2025) · cites this paper as Harbour et al., 2012
VPS35 binds to multiple LFa repeats in FAM21 tail and this interaction is suggested to be sufficient and essential to recruit WASH complex to endosomes.
“The retromer subunit VPS35 binds to multiple LFa repeats in the FAM21 tail and this interaction is suggested to be sufficient and essential to recruit the WASH complex to endosomes20, 21.”
From Retriever is a multiprotein complex for retromer-independent endosomal cargo recycling (2017) · cites this paper as [20]
FAM21 and WASH complex are recruited to endosomes through retromer-dependent and retromer-independent mechanisms.
“FAM21 and the WASH complex are therefore recruited to endosomes through retromer-dependent20, 21 and retromer-independent mechanism(s).”
From Retriever is a multiprotein complex for retromer-independent endosomal cargo recycling (2017) · cites this paper as [20]
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Metadata
- Authors
- Harbour, M. E., Breusegem, S. Y., & Seaman, M. N. J.
- Affiliations
- Cambridge Institute for Medical Research (CIMR)/Department of Clinical Biochemistry, University of Cambridge, Addenbrookes Hospital, Cambridge CB2 0XY, U.K.
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2012-01-27
- Volume
- 442
- Issue
- 1
- Pages
- 209-220
- ISSN
- 0264-6021
- 1470-8728
- Cited by
- 238
- References
- 1
- Language
- en
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