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WASH and WAVE actin regulators of the Wiskott–Aldrich syndrome protein (WASP) family are controlled by analogous structurally related complexes
Abstract
We recently showed that the Wiskott–Aldrich syndrome protein (WASP) family member, WASH, localizes to endosomal subdomains and regulates endocytic vesicle scission in an Arp2/3-dependent manner. Mechanisms regulating WASH activity are unknown. Here we show that WASH functions in cells within a 500 kDa core complex containing Strumpellin, FAM21, KIAA1033 (SWIP), and CCDC53. Although recombinant WASH is constitutively active toward the Arp2/3 complex, the reconstituted core assembly is inhibited, suggesting that it functions in cells to regulate actin dynamics through WASH. FAM21 interacts directly with CAPZ and inhibits its actin-capping activity. Four of the five core components show distant (approximately 15% amino acid sequence identify) but significant structural homology to components of a complex that negatively regulates the WASP family member, WAVE. Moreover, biochemical and electron microscopic analyses show that the WASH and WAVE complexes are structurally similar. Thus, these two distantly related WASP family members are controlled by analogous structurally related mechanisms. Strumpellin is mutated in the human disease hereditary spastic paraplegia, and its link to WASH suggests that misregulation of actin dynamics on endosomes may play a role in this disorder.
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Models of the stoichiometry of the WASH complex suggest that there is 1 strumpellin molecule in the complex.
“Models of the stoichiometry of the WASH complex suggest that there is 1 strumpellin molecule in the complex [9,15].”
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 [15]
The Results and Discussion identify Strumpellin as part of a five-protein WASH core complex. They do not specify the stoichiometry or state that the complex contains exactly one Strumpellin molecule (no page number is available in our copy). (LLM, conf=0.83)
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 [40]
FAM21 has two basic regions within its extended C-terminal tail that interact with PI(3)P and other PIs.
“FAM21 has two basic regions within its extended C-terminal tail that have been shown to interact with PI(3)P and other PIs40”
From Endosomal PI(3)P regulation by the COMMD/CCDC22/CCDC93 (CCC) complex controls membrane protein recycling (2019) · cites this paper as [40]
Jia et al. also found that mutant strumpellin could support WASH complex formation.
“These results support those of Jia et al., who also found that mutant strumpellin could support WASH complex formation [15].”
Strumpellin is a core component of the WASH complex that activates Arp2/3-mediated actin polymerization on endosomes.
“WASHC5, commonly called strumpellin, is a core component of the Wiskott-Aldrich syndrome protein and SCAR homologue (WASH) complex that activates actin nucleation at endosomes.”
From Hereditary spastic paraplegia SPG8 mutations impair CAV1-dependent, integrin-mediated cell adhesion (2020) · cites this paper as [9]
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Research works printed but not linked: 30
- 10.1038/nrm2069 · DOI · Paper page
- 10.1073/pnas.0406472102 · DOI
- 10.1038/nature00859 · DOI · Paper page
- 10.1016/j.ceb.2005.12.003 · DOI
- 10.1002/cm.20342 · DOI
- 10.1038/nsmb.1587 · DOI
- 10.1371/journal.pgen.0030237 · DOI
- 10.1016/j.devcel.2009.09.009 · DOI · Paper page
- 10.1006/meth.2001.1183 · DOI
- 10.1016/S1937-6448(08)00604-7 · DOI
- 10.1042/BJ20050387 · DOI
- 10.1126/science.1091403 · DOI
- 10.1371/journal.pgen.0010017 · DOI
- 10.1016/S1474-4422(08)70258-8 · DOI · Paper page
- 10.1086/510782 · DOI · Paper page
- 10.1016/S0022-2836(05)80360-2 · DOI · Paper page
- 10.1093/nar/25.17.3389 · DOI · Paper page
- 10.1093/nar/gki408 · DOI
- 10.1126/science.252.5009.1162 · DOI · Paper page
- 10.1242/dev.035246 · DOI
- 10.1016/j.devcel.2009.09.010 · DOI · Paper page
- 10.1038/ncb1105 · DOI
- 10.1128/MCB.24.11.4979-4993.2004 · DOI · Paper page
- 10.1242/dev.01274 · DOI
- 10.1073/pnas.0703196104 · DOI
- 10.1038/nrm2330 · DOI · Paper page
- 10.1007/s12026-008-8086-1 · DOI
- 10.1016/j.cell.2006.12.049 · DOI
- 10.1016/j.cell.2008.04.011 · DOI
- 10.1006/jsbi.1999.4174 · DOI
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Metadata
- Authors
- Jia, D., Gomez, T. S., Metlagel, Z., Umetani, J., Otwinowski, Z., Rosen, M. K., & Billadeau, D. D.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-05-24
- Volume
- 107
- Issue
- 23
- Pages
- 10442-10447
- ISSN
- 0027-8424
- 1091-6490
- Cited by
- 232
- References
- 0
- Language
- en
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