WASL (gene) explained

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

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]

Diseases associated with WASL include Wiskottt-Aldrich Syndrome and Vaccinia.^[5]

Interactions

WASL (gene) has been shown to interact with:

• CDC42,^[6]
• Cortactin^[7]
• NCK1,^[8]
• Profilin 1,^{[9] [10]} and
• RHOQ.^[11]

References

Further reading

• Ramesh N, Antón IM, Martínez-Quiles N, Geha RS . Waltzing with WASP . Trends in Cell Biology . 9 . 1 . 15–9 . Jan 1999 . 10087612 . 10.1016/S0962-8924(98)01411-1 .
• Carlier MF, Ducruix A, Pantaloni D . Signalling to actin: the Cdc42-N-WASP-Arp2/3 connection . Chemistry & Biology . 6 . 9 . R235–40 . Sep 1999 . 10467124 . 10.1016/S1074-5521(99)80107-0 . free .
• Suzuki T, Miki H, Takenawa T, Sasakawa C . Neural Wiskott–Aldrich syndrome protein is implicated in the actin-based motility of Shigella flexneri . The EMBO Journal . 17 . 10 . 2767–76 . May 1998 . 9582270 . 1170617 . 10.1093/emboj/17.10.2767 .
• Suetsugu S, Miki H, Takenawa T . The essential role of profilin in the assembly of actin for microspike formation . The EMBO Journal . 17 . 22 . 6516–26 . Nov 1998 . 9822597 . 1170999 . 10.1093/emboj/17.22.6516 .
• Qualmann B, Roos J, DiGregorio PJ, Kelly RB . Syndapin I, a synaptic dynamin-binding protein that associates with the neural Wiskott–Aldrich syndrome protein . Molecular Biology of the Cell . 10 . 2 . 501–13 . Feb 1999 . 9950691 . 25183 . 10.1091/mbc.10.2.501 .
• Suetsugu S, Miki H, Takenawa T . Identification of two human WAVE/SCAR homologues as general actin regulatory molecules which associate with the Arp2/3 complex . Biochemical and Biophysical Research Communications . 260 . 1 . 296–302 . Jun 1999 . 10381382 . 10.1006/bbrc.1999.0894 .
• Egile C, Loisel TP, Laurent V, Li R, Pantaloni D, Sansonetti PJ, Carlier MF . 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 . The Journal of Cell Biology . 146 . 6 . 1319–32 . Sep 1999 . 10491394 . 2156126 . 10.1083/jcb.146.6.1319 .
• Higgs HN, Blanchoin L, Pollard TD . Influence of the C terminus of Wiskott–Aldrich syndrome protein (WASp) and the Arp2/3 complex on actin polymerization . Biochemistry . 38 . 46 . 15212–22 . Nov 1999 . 10563804 . 10.1021/bi991843 .
• Qualmann B, Kelly RB . Syndapin isoforms participate in receptor-mediated endocytosis and actin organization . The Journal of Cell Biology . 148 . 5 . 1047–62 . Mar 2000 . 10704453 . 2174535 . 10.1083/jcb.148.5.1047 .
• Kim AS, Kakalis LT, Abdul-Manan N, Liu GA, Rosen MK . Autoinhibition and activation mechanisms of the Wiskott–Aldrich syndrome protein . Nature . 404 . 6774 . 151–8 . Mar 2000 . 10724160 . 10.1038/35004513 . 2000Natur.404..151K . 4416185 .
• Carlier MF, Nioche P, Broutin-L'Hermite I, Boujemaa R, Le Clainche C, Egile C, Garbay C, Ducruix A, Sansonetti P, Pantaloni D . GRB2 links signaling to actin assembly by enhancing interaction of neural Wiskott–Aldrich syndrome protein (N-WASp) with actin-related protein (ARP2/3) complex . The Journal of Biological Chemistry . 275 . 29 . 21946–52 . Jul 2000 . 10781580 . 10.1074/jbc.M000687200 . free .
• Mimuro H, Suzuki T, Suetsugu S, Miki H, Takenawa T, Sasakawa C . Profilin is required for sustaining efficient intra- and intercellular spreading of Shigella flexneri . The Journal of Biological Chemistry . 275 . 37 . 28893–901 . Sep 2000 . 10867004 . 10.1074/jbc.M003882200 . free .
• Prehoda KE, Scott JA, Mullins RD, Lim WA . Integration of multiple signals through cooperative regulation of the N-WASP-Arp2/3 complex . Science . 290 . 5492 . 801–6 . Oct 2000 . 11052943 . 10.1126/science.290.5492.801 . 2000Sci...290..801P .
• Modregger J, Ritter B, Witter B, Paulsson M, Plomann M . All three PACSIN isoforms bind to endocytic proteins and inhibit endocytosis . Journal of Cell Science . 113 . 24 . 4511–21 . Dec 2000 . 10.1242/jcs.113.24.4511 . 11082044 .
• Marchand JB, Kaiser DA, Pollard TD, Higgs HN . Interaction of WASP/Scar proteins with actin and vertebrate Arp2/3 complex . Nature Cell Biology . 3 . 1 . 76–82 . Jan 2001 . 11146629 . 10.1038/35050590 . 30437883 .
• Fukuoka M, Suetsugu S, Miki H, Fukami K, Endo T, Takenawa T . A novel neural Wiskott–Aldrich syndrome protein (N-WASP) binding protein, WISH, induces Arp2/3 complex activation independent of Cdc42 . The Journal of Cell Biology . 152 . 3 . 471–82 . Feb 2001 . 11157975 . 2196001 . 10.1083/jcb.152.3.471 .

Notes and References

1. Miki H, Sasaki T, Takai Y, Takenawa T . Induction of filopodium formation by a WASP-related actin-depolymerizing protein N-WASP . Nature . 391 . 6662 . 93–6 . Jan 1998 . 9422512 . 10.1038/34208 . 1998Natur.391...93M . 4363890 .
2. Fukuoka M, Miki H, Takenawa T . Identification of N-WASP homologs in human and rat brain . Gene . 196 . 1–2 . 43–8 . Sep 1997 . 9322739 . 10.1016/S0378-1119(97)00184-4 .
3. Web site: Entrez Gene: WASL Wiskott–Aldrich syndrome-like.
4. Suetsugu S, Tezuka T, Morimura T, Hattori M, Mikoshiba K, Yamamoto T, Takenawa T . Regulation of actin cytoskeleton by mDab1 through N-WASP and ubiquitination of mDab1 . The Biochemical Journal . 384 . Pt 1 . 1–8 . Nov 2004 . 15361067 . 1134082 . 10.1042/BJ20041103 .
5. Web site: WASL Gene - GeneCards WASL Protein WASL Antibody. 2018-11-25. www.genecards.org.
6. Carlier MF, Nioche P, Broutin-L'Hermite I, Boujemaa R, Le Clainche C, Egile C, Garbay C, Ducruix A, Sansonetti P, Pantaloni D . GRB2 links signaling to actin assembly by enhancing interaction of neural Wiskott–Aldrich syndrome protein (N-WASp) with actin-related protein (ARP2/3) complex . The Journal of Biological Chemistry . 275 . 29 . 21946–52 . Jul 2000 . 10781580 . 10.1074/jbc.M000687200 . free .
7. Mizutani K, Miki H, He H, Maruta H, Takenawa T . Essential role of neural Wiskott–Aldrich syndrome protein in podosome formation and degradation of extracellular matrix in src-transformed fibroblasts . Cancer Research . 62 . 3 . 669–74 . Feb 2002 . 11830518 .
8. Rohatgi R, Nollau P, Ho HY, Kirschner MW, Mayer BJ . Nck and phosphatidylinositol 4,5-bisphosphate synergistically activate actin polymerization through the N-WASP-Arp2/3 pathway . The Journal of Biological Chemistry . 276 . 28 . 26448–52 . Jul 2001 . 11340081 . 10.1074/jbc.M103856200 . free .
9. Mimuro H, Suzuki T, Suetsugu S, Miki H, Takenawa T, Sasakawa C . Profilin is required for sustaining efficient intra- and intercellular spreading of Shigella flexneri . The Journal of Biological Chemistry . 275 . 37 . 28893–901 . Sep 2000 . 10867004 . 10.1074/jbc.M003882200 . free .
10. Suetsugu S, Miki H, Takenawa T . The essential role of profilin in the assembly of actin for microspike formation . The EMBO Journal . 17 . 22 . 6516–26 . Nov 1998 . 9822597 . 1170999 . 10.1093/emboj/17.22.6516 .
11. Abe T, Kato M, Miki H, Takenawa T, Endo T . Small GTPase Tc10 and its homologue RhoT induce N-WASP-mediated long process formation and neurite outgrowth . Journal of Cell Science . 116 . Pt 1 . 155–68 . Jan 2003 . 12456725 . 10.1242/jcs.00208. free .