WASL (gene)

Wiskott-Aldrich syndrome-like
Rendering of WASL from PDB 2FF3
Available structures PDB 2FF3, 2VCP
Identifiers
Symbols	WASL; DKFZp779G0847; MGC48327; N-WASP; NWASP
External IDs	OMIM: 605056 MGI: 1920428 HomoloGene: 74515 GeneCards: WASL Gene
Gene Ontology Molecular function • actin binding • small GTPase regulator activity • protein binding Cellular component • nucleus • nucleolus • cytoplasm • cytosol • plasma membrane • actin cytoskeleton • lamellipodium Biological process • regulation of transcription, DNA-dependent • protein complex assembly • cellular component movement • axon guidance • actin polymerization or depolymerization • response to bacterium • nitric oxide metabolic process • regulation of nitric-oxide synthase activity Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8976	73178
Ensembl	ENSG00000106299	ENSMUSG00000029684
UniProt	O00401	Q05CX6
RefSeq (mRNA)	NM_003941	NM_028459
RefSeq (protein)	NP_003932	NP_082735
Location (UCSC)	Chr 7: 123.32 – 123.39 Mb	Chr 6: 24.56 – 24.61 Mb
PubMed search	[1]	[2]

Neural Wiskott-Aldrich syndrome protein is a protein that in humans is encoded by the WASL gene.^[1][2][3]

The Wiskott-Aldrich syndrome (WAS) family of proteins share similar domain structure, and are involved in transduction of signals from receptors on the cell surface to the actin cytoskeleton. The presence of a number of different motifs suggests that they are regulated by a number of different stimuli, and interact with multiple proteins. Recent studies have demonstrated that these proteins, directly or indirectly, associate with the small GTPase, Cdc42, known to regulate formation of actin filaments, and the cytoskeletal organizing complex, Arp2/3. The WASL gene product is a homolog of WAS protein, however, unlike the latter, it is ubiquitously expressed and shows highest expression in neural tissues. It has been shown to bind Cdc42 directly, and induce formation of long actin microspikes.^[3]

According to one study, mouse DAB1 regulates actin cytoskeleton through N-WASP.^[4]

Interactions

WASL (gene) has been shown to interact with RHOQ,^[5] NCK1,^[6] Profilin 1,^[7][8] Cortactin^[9] and CDC42.^[1][10]

References

1. ^ ^{a b} Miki H, Sasaki T, Takai Y, Takenawa T (Jan 1998). "Induction of filopodium formation by a WASP-related actin-depolymerizing protein N-WASP". Nature 391 (6662): 93–6. doi:10.1038/34208. PMID 9422512. 
2. ^ Fukuoka M, Miki H, Takenawa T (Oct 1997). "Identification of N-WASP homologs in human and rat brain". Gene 196 (1–2): 43–8. doi:10.1016/S0378-1119(97)00184-4. PMID 9322739. 
3. ^ ^{a b} "Entrez Gene: WASL Wiskott-Aldrich syndrome-like". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8976. 
4. ^ Suetsugu S, Tezuka T, Morimura T, Hattori M, Mikoshiba K, Yamamoto T, Takenawa T (November 2004). "Regulation of actin cytoskeleton by mDab1 through N-WASP and ubiquitination of mDab1". Biochem. J. 384 (Pt 1): 1–8. doi:10.1042/BJ20041103. PMC 1134082. PMID 15361067. http://www.biochemj.org/bj/384/0001/bj3840001.htm. 
5. ^ Abe, Tomoyuki; Kato Masayoshi, Miki Hiroaki, Takenawa Tadaomi, Endo Takeshi (Jan. 2003). "Small GTPase Tc10 and its homologue RhoT induce N-WASP-mediated long process formation and neurite outgrowth". J. Cell. Sci. (England) 116 (Pt 1): 155–68. doi:10.1242/jcs.00208. ISSN 0021-9533. PMID 12456725. 
6. ^ Rohatgi, R; Nollau P, Ho H Y, Kirschner M W, Mayer B J (Jul. 2001). "Nck and phosphatidylinositol 4,5-bisphosphate synergistically activate actin polymerization through the N-WASP-Arp2/3 pathway". J. Biol. Chem. (United States) 276 (28): 26448–52. doi:10.1074/jbc.M103856200. ISSN 0021-9258. PMID 11340081. 
7. ^ Mimuro, H; Suzuki T, Suetsugu S, Miki H, Takenawa T, Sasakawa C (Sep. 2000). "Profilin is required for sustaining efficient intra- and intercellular spreading of Shigella flexneri". J. Biol. Chem. (UNITED STATES) 275 (37): 28893–901. doi:10.1074/jbc.M003882200. ISSN 0021-9258. PMID 10867004. 
8. ^ Suetsugu, S; Miki H, Takenawa T (Nov. 1998). "The essential role of profilin in the assembly of actin for microspike formation". EMBO J. (ENGLAND) 17 (22): 6516–26. doi:10.1093/emboj/17.22.6516. ISSN 0261-4189. PMC 1170999. PMID 9822597. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1170999. 
9. ^ Mizutani, Kiyohito; Miki Hiroaki, He Hong, Maruta Hiroshi, Takenawa Tadaomi (Feb. 2002). "Essential role of neural Wiskott-Aldrich syndrome protein in podosome formation and degradation of extracellular matrix in src-transformed fibroblasts". Cancer Res. (United States) 62 (3): 669–74. ISSN 0008-5472. PMID 11830518. 
10. ^ Carlier, M F; Nioche P, Broutin-L'Hermite I, Boujemaa R, Le Clainche C, Egile C, Garbay C, Ducruix A, Sansonetti P, Pantaloni D (Jul. 2000). "GRB2 links signaling to actin assembly by enhancing interaction of neural Wiskott-Aldrich syndrome protein (N-WASp) with actin-related protein (ARP2/3) complex". J. Biol. Chem. (UNITED STATES) 275 (29): 21946–52. doi:10.1074/jbc.M000687200. ISSN 0021-9258. PMID 10781580. 

Further reading

• Ramesh N, Antón IM, Martínez-Quiles N, Geha RS (1999). "Waltzing with WASP". Trends Cell Biol. 9 (1): 15–9. doi:10.1016/S0962-8924(98)01411-1. PMID 10087612. 
• Carlier MF, Ducruix A, Pantaloni D (1999). "Signalling to actin: the Cdc42-N-WASP-Arp2/3 connection". Chem. Biol. 6 (9): R235–40. doi:10.1016/S1074-5521(99)80107-0. PMID 10467124. 
• Suzuki T, Miki H, Takenawa T, Sasakawa C (1998). "Neural Wiskott-Aldrich syndrome protein is implicated in the actin-based motility of Shigella flexneri". EMBO J. 17 (10): 2767–76. doi:10.1093/emboj/17.10.2767. PMC 1170617. PMID 9582270. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1170617. 
• Suetsugu S, Miki H, Takenawa T (1999). "The essential role of profilin in the assembly of actin for microspike formation". EMBO J. 17 (22): 6516–26. doi:10.1093/emboj/17.22.6516. PMC 1170999. PMID 9822597. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1170999. 
• Qualmann B, Roos J, DiGregorio PJ, Kelly RB (1999). "Syndapin I, a Synaptic Dynamin-binding Protein that Associates with the Neural Wiskott-Aldrich Syndrome Protein". Mol. Biol. Cell 10 (2): 501–13. PMC 25183. PMID 9950691. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=25183. 
• Suetsugu S, Miki H, Takenawa T (1999). "Identification of two human WAVE/SCAR homologues as general actin regulatory molecules which associate with the Arp2/3 complex". Biochem. Biophys. Res. Commun. 260 (1): 296–302. doi:10.1006/bbrc.1999.0894. PMID 10381382. 
• Egile C, Loisel TP, Laurent V, et al. (1999). "Activation of the Cdc42 Effector N-Wasp by the Shigella flexneri Icsa Protein Promotes Actin Nucleation by Arp2/3 Complex and Bacterial Actin-Based Motility". J. Cell Biol. 146 (6): 1319–32. doi:10.1083/jcb.146.6.1319. PMC 2156126. PMID 10491394. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2156126. 
• Higgs HN, Blanchoin L, Pollard TD (1999). "Influence of the C terminus of Wiskott-Aldrich syndrome protein (WASp) and the Arp2/3 complex on actin polymerization". Biochemistry 38 (46): 15212–22. doi:10.1021/bi991843. PMID 10563804. 
• Qualmann B, Kelly RB (2000). "Syndapin Isoforms Participate in Receptor-Mediated Endocytosis and Actin Organization". J. Cell Biol. 148 (5): 1047–62. doi:10.1083/jcb.148.5.1047. PMC 2174535. PMID 10704453. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2174535. 
• Kim AS, Kakalis LT, Abdul-Manan N, et al. (2000). "Autoinhibition and activation mechanisms of the Wiskott-Aldrich syndrome protein". Nature 404 (6774): 151–8. doi:10.1038/35004513. PMID 10724160. 
• Carlier MF, Nioche P, Broutin-L'Hermite I, et al. (2000). "GRB2 links signaling to actin assembly by enhancing interaction of neural Wiskott-Aldrich syndrome protein (N-WASp) with actin-related protein (ARP2/3) complex". J. Biol. Chem. 275 (29): 21946–52. doi:10.1074/jbc.M000687200. PMID 10781580. 
• Mimuro H, Suzuki T, Suetsugu S, et al. (2000). "Profilin is required for sustaining efficient intra- and intercellular spreading of Shigella flexneri". J. Biol. Chem. 275 (37): 28893–901. doi:10.1074/jbc.M003882200. PMID 10867004. 
• Prehoda KE, Scott JA, Mullins RD, Lim WA (2000). "Integration of multiple signals through cooperative regulation of the N-WASP-Arp2/3 complex". Science 290 (5492): 801–6. doi:10.1126/science.290.5492.801. PMID 11052943. 
• Modregger J, Ritter B, Witter B, et al. (2001). "All three PACSIN isoforms bind to endocytic proteins and inhibit endocytosis". J. Cell. Sci. 113 Pt 24: 4511–21. PMID 11082044. 
• Marchand JB, Kaiser DA, Pollard TD, Higgs HN (2001). "Interaction of WASP/Scar proteins with actin and vertebrate Arp2/3 complex". Nat. Cell Biol. 3 (1): 76–82. doi:10.1038/35050590. PMID 11146629. 
• Fukuoka M, Suetsugu S, Miki H, et al. (2001). "A Novel Neural Wiskott-Aldrich Syndrome Protein (N-Wasp) Binding Protein, Wish, Induces Arp2/3 Complex Activation Independent of Cdc42". J. Cell Biol. 152 (3): 471–82. doi:10.1083/jcb.152.3.471. PMC 2196001. PMID 11157975. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2196001.