WASHC5

Summary

Gene Symbol: WASHC5
Description: WASH complex subunit 5
Alias: KIAA0196, RTSC, RTSC1, SPG8, WASH complex subunit 5, WASH complex subunit strumpellin, strumpellin
Species: human
Products:     WASHC5

Top Publications

  1. Clemen C, Tangavelou K, Strucksberg K, Just S, Gaertner L, Regus Leidig H, et al. Strumpellin is a novel valosin-containing protein binding partner linking hereditary spastic paraplegia to protein aggregation diseases. Brain. 2010;133:2920-41 pubmed publisher
    ..We identified strumpellin as a novel valosin-containing protein binding partner...
  2. Helfer E, Harbour M, Henriot V, Lakisic G, Sousa Blin C, Volceanov L, et al. Endosomal recruitment of the WASH complex: active sequences and mutations impairing interaction with the retromer. Biol Cell. 2013;105:191-207 pubmed publisher
    ..The interaction between these two endosomal machineries, the WASH complex and the retromer, is likely to play a critical role in forming platforms at the surface of endosomes for efficient sorting of cargoes. ..
  3. Valdmanis P, Meijer I, Reynolds A, Lei A, Macleod P, Schlesinger D, et al. Mutations in the KIAA0196 gene at the SPG8 locus cause hereditary spastic paraplegia. Am J Hum Genet. 2007;80:152-61 pubmed
    ..are strictly conserved across species and likely have a notable effect on the structure of the protein product strumpellin. Rescue studies with human mRNA injected in zebrafish treated with morpholino oligonucleotides to knock down ..
  4. Freeman C, Seaman M, Reid E. The hereditary spastic paraplegia protein strumpellin: characterisation in neurons and of the effect of disease mutations on WASH complex assembly and function. Biochim Biophys Acta. 2013;1832:160-73 pubmed publisher
    Mutations in the gene encoding strumpellin cause autosomal dominant hereditary spastic paraplegia (HSP), in which there is degeneration of corticospinal tract axons...
  5. Derivery E, Sousa C, Gautier J, Lombard B, Loew D, Gautreau A. The Arp2/3 activator WASH controls the fission of endosomes through a large multiprotein complex. Dev Cell. 2009;17:712-23 pubmed publisher
    ..Together, these data suggest that the WASH molecular machine, integrating CP with a NPF, controls the fission of endosomes through an interplay between the forces generated by microtubule motors and actin polymerization. ..
  6. Pan Y, Viklund I, Tsai H, Pettersson S, Maruyama I. The ulcerative colitis marker protein WAFL interacts with accessory proteins in endocytosis. Int J Biol Sci. 2010;6:163-71 pubmed
    ..Among four proteins found to specifically interact with WAFL, both KIAA0196 and KIAA1033 bind to alpha-appendage of the adaptor protein complex 2 (AP2), which acts as an interaction hub for ..
  7. Harbour M, Breusegem S, Antrobus R, Freeman C, Reid E, Seaman M. The cargo-selective retromer complex is a recruiting hub for protein complexes that regulate endosomal tubule dynamics. J Cell Sci. 2010;123:3703-17 pubmed publisher
    ..One of the retromer-interacting proteins, strumpellin, is mutated in hereditary spastic paraplegia, a progressive length-dependent axonopathy...
  8. Elert Dobkowska E, Stepniak I, Krysa W, Ziora Jakutowicz K, Rakowicz M, Sobanska A, et al. Next-generation sequencing study reveals the broader variant spectrum of hereditary spastic paraplegia and related phenotypes. Neurogenetics. 2019;20:27-38 pubmed publisher
    ..and those of uncertain significance (VUS) in the following genes: SPAST (spastin, SPG4), ATL1 (atlastin 1, SPG3), WASHC5 (SPG8), KIF5A (SPG10), KIF1A (SPG30), SPG11 (spatacsin), CYP27A1, SETX and ITPR1...
  9. Zhao J, Hedera P. Strumpellin and Spartin, Hereditary Spastic Paraplegia Proteins, are Binding Partners. J Exp Neurosci. 2015;9:15-25 pubmed publisher
    ..Here we report interactions of endogenous and overexpressed strumpellin with another HSP-associated protein, spartin...

More Information

Publications30

  1. Verboon J, Rahe T, Rodriguez Mesa E, Parkhurst S. Wash functions downstream of Rho1 GTPase in a subset of Drosophila immune cell developmental migrations. Mol Biol Cell. 2015;26:1665-74 pubmed publisher
    ..complex, whose activity is needed for this migration, whereas members of the WASH regulatory complex (SWIP, Strumpellin, and CCDC53) are not...
  2. Song L, Rijal R, Karow M, Stumpf M, Hahn O, Park L, et al. Expression of N471D strumpellin leads to defects in the endolysosomal system. Dis Model Mech. 2018;11: pubmed publisher
    ..The N471D and several other point mutations of human strumpellin (Str; also known as WASHC5), a member of the Wiskott-Aldrich syndrome protein and SCAR homologue (WASH) complex,..
  3. Duz M, Dasdemir S, Kalayci Yigin A, Akalin M, Seven M. Three novel mutations in 20 patients with hereditary spastic paraparesis. Neurol Sci. 2018;39:1551-1557 pubmed publisher
    ..In this approach, as previously reported c.1859 T > C mutation in KIAA0196 was detected, and it was confirmed with the patient's relatives by SS...
  4. Jahic A, Kreuz F, Zacher P, Fiedler J, Bier A, Reif S, et al. A novel strumpellin mutation and potential pitfalls in the molecular diagnosis of hereditary spastic paraplegia type SPG8. J Neurol Sci. 2014;347:372-4 pubmed publisher
    ..A total of eight KIAA0196/strumpellin variants have thus far been associated with SPG8, a rare dominant HSP...
  5. Allison R, Edgar J, Pearson G, Rizo T, Newton T, Günther S, et al. Defects in ER-endosome contacts impact lysosome function in hereditary spastic paraplegia. J Cell Biol. 2017;216:1337-1355 pubmed publisher
    ..function, similar lysosomal abnormalities were seen in cellular models lacking the WASH complex component strumpellin or the ER morphogen REEP1...
  6. Jahic A, Khundadze M, Jaenisch N, Schüle R, Klimpe S, Klebe S, et al. The spectrum of KIAA0196 variants, and characterization of a murine knockout: implications for the mutational mechanism in hereditary spastic paraplegia type SPG8. Orphanet J Rare Dis. 2015;10:147 pubmed publisher
    ..A total of nine mutations in KIAA0196, which encodes the WASH regulatory complex (SHRC) member strumpellin, have been reported in SPG8 patients so far...
  7. Porkka K, Tammela T, Vessella R, Visakorpi T. RAD21 and KIAA0196 at 8q24 are amplified and overexpressed in prostate cancer. Genes Chromosomes Cancer. 2004;39:1-10 pubmed
    ..Two genes from chromosomal region 8q24-RAD21 and KIAA0196-showed increased expression in clinical prostate carcinomas and were also amplified in 30-40% of xenografts and ..
  8. Ichinose Y, Koh K, Fukumoto M, Yamashiro N, Kobayashi F, Miwa M, et al. Exome sequencing reveals a novel missense mutation in the KIAA0196 gene in a Japanese patient with SPG8. Clin Neurol Neurosurg. 2016;144:36-8 pubmed publisher
    Exome sequencing revealed a novel missense mutation (c.2152G>A, p.E713K) in the KIAA0196 gene in a Japanese patient with SPG8. To date, only 10 mutations in the KIAA0196 gene have been reported in the world...
  9. Hedera P, Rainier S, Alvarado D, Zhao X, Williamson J, Otterud B, et al. Novel locus for autosomal dominant hereditary spastic paraplegia, on chromosome 8q. Am J Hum Genet. 1999;64:563-9 pubmed
  10. Diekstra F, Van Deerlin V, van Swieten J, Al Chalabi A, Ludolph A, Weishaupt J, et al. C9orf72 and UNC13A are shared risk loci for amyotrophic lateral sclerosis and frontotemporal dementia: a genome-wide meta-analysis. Ann Neurol. 2014;76:120-33 pubmed publisher
    ..A third signal, on chromosome 8q24.13 at the SPG8 locus coding for strumpellin (p = 3...
  11. Wang X, Yang Y, Wang X, Li C, Jia J. A novel KIAA0196 (SPG8) mutation in a Chinese family with spastic paraplegia. Chin Med J (Engl). 2014;127:1987-9 pubmed
  12. Elliott A, Simard L, Coghlan G, Chudley A, Chodirker B, Greenberg C, et al. A novel mutation in KIAA0196: identification of a gene involved in Ritscher-Schinzel/3C syndrome in a First Nations cohort. J Med Genet. 2013;50:819-22 pubmed publisher
    ..A 60% reduction in the amount of strumpellin protein was observed on western blot...
  13. Ryder P, Vistein R, Gokhale A, Seaman M, Puthenveedu M, Faundez V. The WASH complex, an endosomal Arp2/3 activator, interacts with the Hermansky-Pudlak syndrome complex BLOC-1 and its cargo phosphatidylinositol-4-kinase type IIα. Mol Biol Cell. 2013;24:2269-84 pubmed publisher
    ..We conclude that the Hermansky-Pudlak syndrome complex BLOC-1 and its cargo PI4KIIα interact with regulators of the actin cytoskeleton. ..
  14. Bettencourt C, Morris H, Singleton A, Hardy J, Houlden H. Exome sequencing expands the mutational spectrum of SPG8 in a family with spasticity responsive to L-DOPA treatment. J Neurol. 2013;260:2414-6 pubmed publisher
  15. Bartuzi P, Billadeau D, Favier R, Rong S, Dekker D, Fedoseienko A, et al. CCC- and WASH-mediated endosomal sorting of LDLR is required for normal clearance of circulating LDL. Nat Commun. 2016;7:10961 pubmed publisher
    ..Furthermore, a mutation in the WASH component KIAA0196 (strumpellin) is associated with hypercholesterolaemia in humans...
  16. Freeman C, Hesketh G, Seaman M. RME-8 coordinates the activity of the WASH complex with the function of the retromer SNX dimer to control endosomal tubulation. J Cell Sci. 2014;127:2053-70 pubmed publisher
  17. Türk M, Schroder R, Khuller K, Hofmann A, Berwanger C, Ludolph A, et al. Genetic analysis of VCP and WASH complex genes in a German cohort of sporadic ALS-FTD patients. Neurobiol Aging. 2017;56:213.e1-213.e5 pubmed publisher
    ..Next-generation panel sequencing of VCP, WASH1, FAM21C, CCDC53, SWIP, strumpellin, F-actin capping protein of muscle Z-line alfa 1 (CAPZA1), and CAPZB genes was performed in 43 sporadic ALS/FTD ..
  18. Tyrrell B, Woodham E, Spence H, Strathdee D, Insall R, Machesky L. Loss of strumpellin in the melanocytic lineage impairs the WASH Complex but does not affect coat colour. Pigment Cell Melanoma Res. 2016;29:559-71 pubmed publisher
    ..Loss of one of the two subunits WASH or strumpellin in mice is lethal, but little is known about their role in mammals in vivo...
  19. Zavodszky E, Seaman M, Moreau K, Jimenez Sanchez M, Breusegem S, Harbour M, et al. Mutation in VPS35 associated with Parkinson's disease impairs WASH complex association and inhibits autophagy. Nat Commun. 2014;5:3828 pubmed publisher
    ..Thus, the PD-causing D620N mutation in VPS35 restricts WASH complex recruitment to endosomes, and reveals a novel role for the WASH complex in autophagosome formation. ..
  20. de Bot S, Vermeer S, Buijsman W, Heister A, Voorendt M, Verrips A, et al. Pure adult-onset spastic paraplegia caused by a novel mutation in the KIAA0196 (SPG8) gene. J Neurol. 2013;260:1765-9 pubmed publisher
    ..Our purpose was to screen for KIAA0196 (SPG8) mutations in AD-HSP patients and to investigate their phenotype...