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A FAM21-Containing WASH Complex Regulates Retromer-Dependent Sorting
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Mammalian cells lacking strumpellin have an increased number of SNX1- and VPS26-positive endosomal tubules.
“Mammalian cells lacking strumpellin have an increased number of SNX1- and VPS26-positive endosomal tubules [9,10,13].”
From The hereditary spastic paraplegia protein strumpellin: Characterisation in neurons and of the effect of disease mutations on WASH complex assembly and function (2013) · cites this paper as [10]
The Results section, “Retromer-mediated tubulation is exaggerated in the absence of WASH” (page unavailable), reports elongated VPS29-rich endosomal tubules after WASH depletion and describes SNX1 localization to endosomes. It does not establish the claimed increase in SNX1- and VPS26-positive tubules in cells lacking strumpellin; the tested depletion and VPS marker differ. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe WASH complex functions in endocytic recycling, maintenance of endolysosomal network integrity, exocytosis, cell adhesion, and cell migration.
“The WASH complex functions in the endocytic recycling of various types of membrane proteins, maintenance of endolysosomal network integrity, exocytosis, cell adhesion, and cell migration (11-23).”
From Hereditary spastic paraplegia SPG8 mutations impair CAV1-dependent, integrin-mediated cell adhesion (2020) · cites this paper as [12]
The Results section on CI-MPR sorting shows that WASH regulates retromer-dependent transport of a membrane receptor from endosomes toward the Golgi, supporting a role in endosomal recycling. The paper does not establish the broader claims about maintenance of endolysosomal network integrity, exocytosis, cell adhesion, or cell migration; it also reports that WASH is dispensable for TCR and EGFR endocytosis. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe common labelling of the WASH complex by both Retromer and Retriever is consistent with their known biochemical association and physical co-localisation to the retrieval sub-domain and the central role of actin polymerisation and actin turnover in Retromer- and Retriever-dependent cargo sorting.
“Building on this, the common labelling of the WASH complex by both Retromer and Retriever (Fig. 2E) is entirely consistent with their known biochemical association and physical co-localisation to the retrieval sub-domain and the central role of actin polymerisation and actin turnover in Retromer- and Retriever-dependent cargo sorting17,19,24,56–58.”
From Mapping of endosomal proximity proteomes reveals Retromer as a hub for RAB GTPase regulation (2025) · cites this paper as [24]
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Experimental — accuracy not yet measuredWASH serves as an actin nucleation-promoting factor for the ARP2/3 complex, which drives the generation of branched F-actin filaments on endosomal membranes.
“WASH serves as an actin nucleation-promoting factor for the ARP2/3 complex, which drives the generation of branched F-actin filaments on endosomal membranes37–40”
From Endosomal PI(3)P regulation by the COMMD/CCDC22/CCDC93 (CCC) complex controls membrane protein recycling (2019) · cites this paper as [38]
The WASH complex is recruited to endosomes by interactions with the retromer complex.
“Strumpellin is a component of the WASH complex, an actin-regulating complex that is recruited to endosomes by interactions with the retromer complex.”
Cells lacking components of the WASH complex, including strumpellin, have increased endosomal tubulation.
“Thus cells lacking components of the WASH complex, including strumpellin, have increased endosomal tubulation, consistent with a defect in tubule fission from the endosome [9,10,13].”
Strumpellin is a component of the WASH complex.
“Strumpellin is a component of the WASH complex, an actin-regulating complex that is recruited to endosomes by interactions with the retromer complex.”
Cells depleted of other WASH complex components, such as Wash1, also have increased endosomal tubulation.
“Cells depleted of other WASH complex components, such as Wash1, also have increased endosomal tubulation, and this phenotype has been interpreted as a consequence of the loss of a WASH complex-generated pushing force involved in endosomal tubule fission [9,10].”
HeLa cells lacking strumpellin have increased tubulation of the SNX1 and retromer endosomal compartment.
“HeLa cells lacking strumpellin have increased tubulation of the SNX1 and retromer endosomal compartment [10,13].”
Direct binding of FAM21 to VPS35 is a major mechanism for the retromer-dependent association of the WASH complex to endosomes.
“Direct binding of FAM21 to VPS35 is a major mechanism for the retromer-dependent association of the WASH complex to endosomes (Gomez and Billadeau, 2009; Harbour et al., 2010; Jia et al., 2012).”
From Acute inactivation of retromer and ESCPE-1 leads to time-resolved defects in endosomal cargo sorting (2020) · cites this paper as Gomez and Billadeau, 2009
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Research works printed but not linked: 39
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Metadata
- Authors
- Gomez, T. S., & Billadeau, D. D.
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2009-11
- Volume
- 17
- Issue
- 5
- Pages
- 699-711
- ISSN
- 1534-5807
- PMC
- PMC2803077
- Cited by
- 521
- References
- 0
- Language
- en
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1390 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Funders
- National Institutes of Health (NIH-T32-AI07047, R01-AI065474)
- Mayo Foundation for Medical Education and Research
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