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WHIMP links the actin nucleation machinery to Src-family kinase signaling during protrusion and motility


Autoři: Shail Kabrawala aff001;  Margaret D. Zimmer aff001;  Kenneth G. Campellone aff001
Působiště autorů: Department of Molecular and Cell Biology, Institute for Systems Genomics, University of Connecticut, Storrs, Connecticut, United States of America aff001
Vyšlo v časopise: WHIMP links the actin nucleation machinery to Src-family kinase signaling during protrusion and motility. PLoS Genet 16(3): e32767. doi:10.1371/journal.pgen.1008694
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008694

Souhrn

Cell motility is governed by cooperation between the Arp2/3 complex and nucleation-promoting factors from the Wiskott-Aldrich Syndrome Protein (WASP) family, which together assemble actin filament networks to drive membrane protrusion. Here we identify WHIMP (WAVE Homology In Membrane Protrusions) as a new member of the WASP family. The Whimp gene is encoded on the X chromosome of a subset of mammals, including mice. Murine WHIMP promotes Arp2/3-dependent actin assembly, but is less potent than other nucleation factors. Nevertheless, WHIMP-mediated Arp2/3 activation enhances both plasma membrane ruffling and wound healing migration, whereas WHIMP depletion impairs protrusion and slows motility. WHIMP expression also increases Src-family kinase activity, and WHIMP-induced ruffles contain the additional nucleation-promoting factors WAVE1, WAVE2, and N-WASP, but not JMY or WASH. Perturbing the function of Src-family kinases, WAVE proteins, or Arp2/3 complex inhibits WHIMP-driven ruffling. These results suggest that WHIMP-associated actin assembly plays a direct role in membrane protrusion, but also results in feedback control of tyrosine kinase signaling to modulate the activation of multiple WASP-family members.

Klíčová slova:

Actin polymerization – Actins – Cell membranes – Cell motility – Cell staining – DAPI staining – Nucleation – Small interfering RNAs


Zdroje

1. Pollard TD, Cooper JA. Actin, a central player in cell shape and movement. Science. 2009;326(5957):1208–12. Epub 2009/12/08. 326/5957/1208 doi: 10.1126/science.1175862 19965462.

2. Rotty JD, Wu C, Bear JE. New insights into the regulation and cellular functions of the ARP2/3 complex. Nature reviews Molecular cell biology. 2013;14(1):7–12. Epub 2012/12/06. doi: 10.1038/nrm3492 23212475.

3. Campellone KG, Welch MD. A nucleator arms race: cellular control of actin assembly. Nature reviews Molecular cell biology. 2010;11(4):237–51. Epub 2010/03/20. doi: 10.1038/nrm2867 20237478.

4. Alekhina O, Burstein E, Billadeau DD. Cellular functions of WASP family proteins at a glance. Journal of cell science. 2017;130(14):2235–41. doi: 10.1242/jcs.199570 28646090

5. Rottner K, Schaks M. Assembling actin filaments for protrusion. Current opinion in cell biology. 2019;56:53–63. doi: 10.1016/j.ceb.2018.09.004 30278304.

6. Dominguez R. The WH2 Domain and Actin Nucleation: Necessary but Insufficient. Trends Biochem Sci. 2016;41(6):478–90. doi: 10.1016/j.tibs.2016.03.004 27068179

7. Boczkowska M, Rebowski G, Kast DJ, Dominguez R. Structural analysis of the transitional state of Arp2/3 complex activation by two actin-bound WCAs. Nat Commun. 2014;5:3308. doi: 10.1038/ncomms4308 24518936

8. Goley ED, Rodenbusch SE, Martin AC, Welch MD. Critical conformational changes in the Arp2/3 complex are induced by nucleotide and nucleation promoting factor. Mol Cell. 2004;16(2):269–79. Epub 2004/10/21. doi: 10.1016/j.molcel.2004.09.018 15494313.

9. Higgs HN, Pollard TD. Regulation of actin polymerization by Arp2/3 complex and WASp/Scar proteins. The Journal of biological chemistry. 1999;274(46):32531–4. doi: 10.1074/jbc.274.46.32531 10551802.

10. Machesky LM, Insall RH. Scar1 and the related Wiskott-Aldrich syndrome protein, WASP, regulate the actin cytoskeleton through the Arp2/3 complex. Current biology: CB. 1998;8(25):1347–56. Epub 1999/01/16. doi: 10.1016/s0960-9822(98)00015-3 9889097.

11. Mullins RD, Heuser JA, Pollard TD. The interaction of Arp2/3 complex with actin: nucleation, high affinity pointed end capping, and formation of branching networks of filaments. Proceedings of the National Academy of Sciences of the United States of America. 1998;95(11):6181–6. Epub 1998/05/30. doi: 10.1073/pnas.95.11.6181 9600938.

12. Panchal SC, Kaiser DA, Torres E, Pollard TD, Rosen MK. A conserved amphipathic helix in WASP/Scar proteins is essential for activation of Arp2/3 complex. Nat Struct Biol. 2003;10(8):591–8. Epub 2003/07/23. doi: 10.1038/nsb952 12872157.

13. Rodnick-Smith M, Luan Q, Liu SL, Nolen BJ. Role and structural mechanism of WASP-triggered conformational changes in branched actin filament nucleation by Arp2/3 complex. Proceedings of the National Academy of Sciences of the United States of America. 2016;113(27):E3834–43. doi: 10.1073/pnas.1517798113 27325766

14. Helgeson LA, Nolen BJ. Mechanism of synergistic activation of Arp2/3 complex by cortactin and N-WASP. Elife. 2013;2:e00884. Epub 2013/09/10. doi: 10.7554/eLife.00884 24015358.

15. Schnoor M, Stradal TE, Rottner K. Cortactin: Cell Functions of A Multifaceted Actin-Binding Protein. Trends in cell biology. 2018;28(2):79–98. doi: 10.1016/j.tcb.2017.10.009 29162307.

16. Eisenmann KM, Harris ES, Kitchen SM, Holman HA, Higgs HN, Alberts AS. Dia-interacting protein modulates formin-mediated actin assembly at the cell cortex. Current biology: CB. 2007;17(7):579–91. Epub 2007/04/03. doi: 10.1016/j.cub.2007.03.024 17398099.

17. Wagner AR, Luan Q, Liu SL, Nolen BJ. Dip1 defines a class of Arp2/3 complex activators that function without preformed actin filaments. Current biology: CB. 2013;23(20):1990–8. Epub 2013/10/15. doi: 10.1016/j.cub.2013.08.029 24120641.

18. Thrasher AJ, Burns SO. WASP: a key immunological multitasker. Nat Rev Immunol. 2010;10(3):182–92. doi: 10.1038/nri2724 20182458.

19. Dahl JP, Wang-Dunlop J, Gonzales C, Goad ME, Mark RJ, Kwak SP. Characterization of the WAVE1 knock-out mouse: implications for CNS development. J Neurosci. 2003;23(8):3343–52. Epub 2003/04/30. 23/8/3343 doi: 10.1523/JNEUROSCI.23-08-03343.2003 12716942.

20. Snapper SB, Takeshima F, Anton I, Liu CH, Thomas SM, Nguyen D, et al. N-WASP deficiency reveals distinct pathways for cell surface projections and microbial actin-based motility. Nature cell biology. 2001;3(10):897–904. Epub 2001/10/05. doi: 10.1038/ncb1001-897 11584271.

21. Yamazaki D, Suetsugu S, Miki H, Kataoka Y, Nishikawa S, Fujiwara T, et al. WAVE2 is required for directed cell migration and cardiovascular development. Nature. 2003;424(6947):452–6. Epub 2003/07/25. doi: 10.1038/nature01770 12879075.

22. Yan C, Martinez-Quiles N, Eden S, Shibata T, Takeshima F, Shinkura R, et al. WAVE2 deficiency reveals distinct roles in embryogenesis and Rac-mediated actin-based motility. EMBO J. 2003;22(14):3602–12. Epub 2003/07/11. doi: 10.1093/emboj/cdg350 12853475.

23. Machesky LM, Mullins RD, Higgs HN, Kaiser DA, Blanchoin L, May RC, et al. Scar, a WASp-related protein, activates nucleation of actin filaments by the Arp2/3 complex. Proceedings of the National Academy of Sciences of the United States of America. 1999;96(7):3739–44. doi: 10.1073/pnas.96.7.3739 10097107

24. Miki H, Sasaki T, Takai Y, Takenawa T. Induction of filopodium formation by a WASP-related actin-depolymerizing protein N-WASP. Nature. 1998;391(6662):93–6. Epub 1998/01/09. doi: 10.1038/34208 9422512.

25. Miki H, Suetsugu S, Takenawa T. WAVE, a novel WASP-family protein involved in actin reorganization induced by Rac. EMBO J. 1998;17(23):6932–41. Epub 1998/12/08. doi: 10.1093/emboj/17.23.6932 9843499.

26. Rohatgi R, Ma L, Miki H, Lopez M, Kirchhausen T, Takenawa T, et al. The interaction between N-WASP and the Arp2/3 complex links Cdc42-dependent signals to actin assembly. Cell. 1999;97(2):221–31. Epub 1999/04/29. doi: 10.1016/s0092-8674(00)80732-1 10219243.

27. Fritz-Laylin LK, Lord SJ, Mullins RD. WASP and SCAR are evolutionarily conserved in actin-filled pseudopod-based motility. The Journal of cell biology. 2017;216(6):1673–88. doi: 10.1083/jcb.201701074 28473602

28. Linardopoulou EV, Parghi SS, Friedman C, Osborn GE, Parkhurst SM, Trask BJ. Human Subtelomeric WASH Genes Encode a New Subclass of the WASP Family. PLoS Genet. 2007;3(12):e237. Epub 2007/12/28. doi: 10.1371/journal.pgen.0030237 18159949.

29. Gomez TS, Gorman JA, Artal-Martinez de Narvajas A, Koenig AO, Billadeau DD. Trafficking defects in WASH-knockout fibroblasts originate from collapsed endosomal and lysosomal networks. Molecular biology of the cell. 2012;23(16):3215–28. Epub 2012/06/22. doi: 10.1091/mbc.E12-02-0101 22718907.

30. Derivery E, Sousa C, Gautier JJ, Lombard B, Loew D, Gautreau A. The Arp2/3 activator WASH controls the fission of endosomes through a large multiprotein complex. Developmental cell. 2009;17(5):712–23. Epub 2009/11/20. doi: 10.1016/j.devcel.2009.09.010 19922875.

31. Gomez TS, Billadeau DD. A FAM21-containing WASH complex regulates retromer-dependent sorting. Developmental cell. 2009;17(5):699–711. Epub 2009/11/20. doi: 10.1016/j.devcel.2009.09.009 19922874.

32. Duleh SN, Welch MD. WASH and the Arp2/3 complex regulate endosome shape and trafficking. Cytoskeleton (Hoboken). 2010;67(3):193–206. Epub 2010/02/23. doi: 10.1002/cm.20437 20175130.

33. Campellone KG, Webb NJ, Znameroski EA, Welch MD. WHAMM is an Arp2/3 complex activator that binds microtubules and functions in ER to Golgi transport. Cell. 2008;134(1):148–61. Epub 2008/07/11. doi: 10.1016/j.cell.2008.05.032 18614018.

34. Russo AJ, Mathiowetz AJ, Hong S, Welch MD, Campellone KG. Rab1 recruits WHAMM during membrane remodeling but limits actin nucleation. Molecular biology of the cell. 2016;27(6):967–78. doi: 10.1091/mbc.E15-07-0508 26823012

35. Schluter K, Waschbusch D, Anft M, Hugging D, Kind S, Hanisch J, et al. JMY is involved in anterograde vesicle trafficking from the trans-Golgi network. European journal of cell biology. 2014;93(5–6):194–204. doi: 10.1016/j.ejcb.2014.06.001 25015719.

36. Coutts AS, La Thangue NB. Actin nucleation by WH2 domains at the autophagosome. Nat Commun. 2015;6:7888. doi: 10.1038/ncomms8888 26223951

37. Kast DJ, Zajac AL, Holzbaur EL, Ostap EM, Dominguez R. WHAMM Directs the Arp2/3 Complex to the ER for Autophagosome Biogenesis through an Actin Comet Tail Mechanism. Current biology: CB. 2015;25(13):1791–7. doi: 10.1016/j.cub.2015.05.042 26096974

38. Mathiowetz AJ, Baple E, Russo AJ, Coulter AM, Carrano E, Brown JD, et al. An Amish founder mutation disrupts a PI(3)P-WHAMM-Arp2/3 complex-driven autophagosomal remodeling pathway. Molecular biology of the cell. 2017;28(19):2492–507. doi: 10.1091/mbc.E17-01-0022 28720660

39. Duleh SN, Welch MD. Regulation of integrin trafficking, cell adhesion, and cell migration by WASH and the Arp2/3 complex. Cytoskeleton (Hoboken). 2012;69(12):1047–58. doi: 10.1002/cm.21069 23012235

40. Gad AK, Nehru V, Ruusala A, Aspenstrom P. RhoD regulates cytoskeletal dynamics via the actin nucleation-promoting factor WASp homologue associated with actin Golgi membranes and microtubules. Molecular biology of the cell. 2012;23(24):4807–19. Epub 2012/10/23. doi: 10.1091/mbc.E12-07-0555 23087206.

41. Zech T, Calaminus SD, Caswell P, Spence HJ, Carnell M, Insall RH, et al. The Arp2/3 activator WASH regulates alpha5beta1-integrin-mediated invasive migration. Journal of cell science. 2011;124(Pt 22):3753–9. Epub 2011/11/25. doi: 10.1242/jcs.080986 22114305.

42. Zuchero JB, Coutts AS, Quinlan ME, Thangue NB, Mullins RD. p53-cofactor JMY is a multifunctional actin nucleation factor. Nature cell biology. 2009;11(4):451–9. Epub 2009/03/17. doi: 10.1038/ncb1852 19287377.

43. Bear JE, Haugh JM. Directed migration of mesenchymal cells: where signaling and the cytoskeleton meet. Current opinion in cell biology. 2014;30:74–82. doi: 10.1016/j.ceb.2014.06.005 24999834

44. Huveneers S, Danen EH. Adhesion signaling—crosstalk between integrins, Src and Rho. Journal of cell science. 2009;122(Pt 8):1059–69. doi: 10.1242/jcs.039446 19339545.

45. Krause M, Gautreau A. Steering cell migration: lamellipodium dynamics and the regulation of directional persistence. Nature reviews Molecular cell biology. 2014;15(9):577–90. doi: 10.1038/nrm3861 25145849.

46. Lawson CD, Ridley AJ. Rho GTPase signaling complexes in cell migration and invasion. The Journal of cell biology. 2018;217(2):447–57. doi: 10.1083/jcb.201612069 29233866

47. Gardel ML, Schneider IC, Aratyn-Schaus Y, Waterman CM. Mechanical integration of actin and adhesion dynamics in cell migration. Annu Rev Cell Dev Biol. 2010;26:315–33. doi: 10.1146/annurev.cellbio.011209.122036 19575647

48. Kim AS, Kakalis LT, Abdul-Manan N, Liu GA, Rosen MK. Autoinhibition and activation mechanisms of the Wiskott-Aldrich syndrome protein. Nature. 2000;404(6774):151–8. Epub 2000/03/21. doi: 10.1038/35004513 10724160.

49. Prehoda KE, Scott JA, Mullins RD, Lim WA. Integration of multiple signals through cooperative regulation of the N-WASP-Arp2/3 complex. Science. 2000;290(5492):801–6. Epub 2000/10/29. doi: 10.1126/science.290.5492.801 11052943.

50. Rohatgi R, Ho HY, Kirschner MW. Mechanism of N-WASP activation by CDC42 and phosphatidylinositol 4, 5-bisphosphate. The Journal of cell biology. 2000;150(6):1299–310. Epub 2000/09/20. doi: 10.1083/jcb.150.6.1299 10995436.

51. Tomasevic N, Jia Z, Russell A, Fujii T, Hartman JJ, Clancy S, et al. Differential regulation of WASP and N-WASP by Cdc42, Rac1, Nck, and PI(4,5)P2. Biochemistry. 2007;46(11):3494–502. Epub 2007/02/17. doi: 10.1021/bi062152y 17302440.

52. Burton EA, Oliver TN, Pendergast AM. Abl kinases regulate actin comet tail elongation via an N-WASP-dependent pathway. Mol Cell Biol. 2005;25(20):8834–43. doi: 10.1128/MCB.25.20.8834-8843.2005 16199863

53. Cory GO, Garg R, Cramer R, Ridley AJ. Phosphorylation of tyrosine 291 enhances the ability of WASp to stimulate actin polymerization and filopodium formation. Wiskott-Aldrich Syndrome protein. The Journal of biological chemistry. 2002;277(47):45115–21. Epub 2002/09/18. doi: 10.1074/jbc.M203346200 12235133.

54. Miller MM, Lapetina S, MacGrath SM, Sfakianos MK, Pollard TD, Koleske AJ. Regulation of actin polymerization and adhesion-dependent cell edge protrusion by the Abl-related gene (Arg) tyrosine kinase and N-WASp. Biochemistry. 2010;49(10):2227–34. doi: 10.1021/bi901721u 20146487

55. Suetsugu S, Hattori M, Miki H, Tezuka T, Yamamoto T, Mikoshiba K, et al. Sustained activation of N-WASP through phosphorylation is essential for neurite extension. Developmental cell. 2002;3(5):645–58. Epub 2002/11/15. doi: 10.1016/s1534-5807(02)00324-6 12431372.

56. Torres E, Rosen MK. Protein-tyrosine kinase and GTPase signals cooperate to phosphorylate and activate Wiskott-Aldrich syndrome protein (WASP)/neuronal WASP. The Journal of biological chemistry. 2006;281(6):3513–20. Epub 2005/11/19. doi: 10.1074/jbc.M509416200 16293614.

57. Anton IM, Gomez-Oro C, Rivas S, Wandosell F. Crosstalk between WIP and Rho family GTPases. Small GTPases. 2018:1–7. doi: 10.1080/21541248.2017.1390522 29172947.

58. Eden S, Rohatgi R, Podtelejnikov AV, Mann M, Kirschner MW. Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck. Nature. 2002;418(6899):790–3. Epub 2002/08/16. doi: 10.1038/nature00859 12181570.

59. Gautreau A, Ho HY, Li J, Steen H, Gygi SP, Kirschner MW. Purification and architecture of the ubiquitous Wave complex. Proceedings of the National Academy of Sciences of the United States of America. 2004;101(13):4379–83. Epub 2004/04/09. doi: 10.1073/pnas.0400628101 15070726.

60. Chen B, Brinkmann K, Chen Z, Pak CW, Liao Y, Shi S, et al. The WAVE regulatory complex links diverse receptors to the actin cytoskeleton. Cell. 2014;156(1–2):195–207. doi: 10.1016/j.cell.2013.11.048 24439376

61. Chen Z, Borek D, Padrick SB, Gomez TS, Metlagel Z, Ismail AM, et al. Structure and control of the actin regulatory WAVE complex. Nature. 2010;468(7323):533–8. Epub 2010/11/26. doi: 10.1038/nature09623 21107423.

62. Koronakis V, Hume PJ, Humphreys D, Liu T, Horning O, Jensen ON, et al. WAVE regulatory complex activation by cooperating GTPases Arf and Rac1. Proceedings of the National Academy of Sciences of the United States of America. 2011;108(35):14449–54. Epub 2011/08/17. doi: 10.1073/pnas.1107666108 21844371.

63. Lebensohn AM, Kirschner MW. Activation of the WAVE complex by coincident signals controls actin assembly. Mol Cell. 2009;36(3):512–24. Epub 2009/11/18. doi: 10.1016/j.molcel.2009.10.024 19917258.

64. Oikawa T, Yamaguchi H, Itoh T, Kato M, Ijuin T, Yamazaki D, et al. PtdIns(3,4,5)P3 binding is necessary for WAVE2-induced formation of lamellipodia. Nature cell biology. 2004;6(5):420–6. Epub 2004/04/27. doi: 10.1038/ncb1125 15107862.

65. Ardern H, Sandilands E, Machesky LM, Timpson P, Frame MC, Brunton VG. Src-dependent phosphorylation of Scar1 promotes its association with the Arp2/3 complex. Cell motility and the cytoskeleton. 2006;63(1):6–13. doi: 10.1002/cm.20101 16317717.

66. Cestra G, Toomre D, Chang S, De Camilli P. The Abl/Arg substrate ArgBP2/nArgBP2 coordinates the function of multiple regulatory mechanisms converging on the actin cytoskeleton. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(5):1731–6. doi: 10.1073/pnas.0409376102 15659545

67. Leng Y, Zhang J, Badour K, Arpaia E, Freeman S, Cheung P, et al. Abelson-interactor-1 promotes WAVE2 membrane translocation and Abelson-mediated tyrosine phosphorylation required for WAVE2 activation. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(4):1098–103. Epub 2005/01/20. doi: 10.1073/pnas.0409120102 15657136.

68. Stuart JR, Gonzalez FH, Kawai H, Yuan ZM. c-Abl interacts with the WAVE2 signaling complex to induce membrane ruffling and cell spreading. The Journal of biological chemistry. 2006;281(42):31290–7. doi: 10.1074/jbc.M602389200 16899465.

69. Jia D, Gomez TS, Metlagel Z, Umetani J, Otwinowski Z, Rosen MK, et al. WASH and WAVE actin regulators of the Wiskott-Aldrich syndrome protein (WASP) family are controlled by analogous structurally related complexes. Proceedings of the National Academy of Sciences of the United States of America. 2010;107(23):10442–7. Epub 2010/05/26. doi: 10.1073/pnas.0913293107 20498093.

70. Shen QT, Hsiue PP, Sindelar CV, Welch MD, Campellone KG, Wang HW. Structural insights into WHAMM-mediated cytoskeletal coordination during membrane remodeling. The Journal of cell biology. 2012;199(1):111–24. Epub 2012/10/03. doi: 10.1083/jcb.201204010 23027905.

71. Hu X, Mullins RD. LC3 and STRAP regulate actin filament assembly by JMY during autophagosome formation. The Journal of cell biology. 2019;218(1):251–66. doi: 10.1083/jcb.201802157 30420355

72. Marchand JB, Kaiser DA, Pollard TD, Higgs HN. Interaction of WASP/Scar proteins with actin and vertebrate Arp2/3 complex. Nature cell biology. 2001;3(1):76–82. Epub 2001/01/09. doi: 10.1038/35050590 11146629.

73. Kollmar M, Lbik D, Enge S. Evolution of the eukaryotic ARP2/3 activators of the WASP family: WASP, WAVE, WASH, and WHAMM, and the proposed new family members WAWH and WAML. BMC Res Notes. 2012;5:88. Epub 2012/02/10. doi: 10.1186/1756-0500-5-88 22316129.

74. Veltman DM, Insall RH. WASP family proteins: their evolution and its physiological implications. Molecular biology of the cell. 2010;21(16):2880–93. Epub 2010/06/25. doi: 10.1091/mbc.E10-04-0372 20573979.

75. Miki H, Miura K, Takenawa T. N-WASP, a novel actin-depolymerizing protein, regulates the cortical cytoskeletal rearrangement in a PIP2-dependent manner downstream of tyrosine kinases. EMBO J. 1996;15(19):5326–35. Epub 1996/10/01. 8895577.

76. Parolini O, Berardelli S, Riedl E, Bello-Fernandez C, Strobl H, Majdic O, et al. Expression of Wiskott-Aldrich syndrome protein (WASP) gene during hematopoietic differentiation. Blood. 1997;90(1):70–5. 9207440.

77. 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. Biochem Biophys Res Commun. 1999;260(1):296–302. Epub 1999/06/25. doi: 10.1006/bbrc.1999.0894 10381382.

78. Cheeseman IM, Desai A. A combined approach for the localization and tandem affinity purification of protein complexes from metazoans. Sci STKE. 2005;2005(266):pl1. Epub 2005/01/13. doi: 10.1126/stke.2662005pl1 15644491.

79. Firat-Karalar EN, Hsiue PP, Welch MD. The actin nucleation factor JMY is a negative regulator of neuritogenesis. Molecular biology of the cell. 2012;22(23):4563–74. Epub 2011/10/04. doi: 10.1091/mbc.E11-06-0585 21965285.

80. Steffen A, Rottner K, Ehinger J, Innocenti M, Scita G, Wehland J, et al. Sra-1 and Nap1 link Rac to actin assembly driving lamellipodia formation. EMBO J. 2004;23(4):749–59. Epub 2004/02/07. doi: 10.1038/sj.emboj.7600084 14765121.

81. Suetsugu S, Yamazaki D, Kurisu S, Takenawa T. Differential roles of WAVE1 and WAVE2 in dorsal and peripheral ruffle formation for fibroblast cell migration. Developmental cell. 2003;5(4):595–609. Epub 2003/10/11. doi: 10.1016/s1534-5807(03)00297-1 14536061.

82. Innocenti M. New insights into the formation and the function of lamellipodia and ruffles in mesenchymal cell migration. Cell Adh Migr. 2018;12(5):401–16. doi: 10.1080/19336918.2018.1448352 29513145

83. Hanke JH, Gardner JP, Dow RL, Changelian PS, Brissette WH, Weringer EJ, et al. Discovery of a novel, potent, and Src family-selective tyrosine kinase inhibitor. Study of Lck- and FynT-dependent T cell activation. The Journal of biological chemistry. 1996;271(2):695–701.

84. Hennequin LF, Allen J, Breed J, Curwen J, Fennell M, Green TP, et al. N-(5-chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5- (tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine, a novel, highly selective, orally available, dual-specific c-Src/Abl kinase inhibitor. J Med Chem. 2006;49(22):6465–88. doi: 10.1021/jm060434q 17064066.

85. Derry JM, Ochs HD, Francke U. Isolation of a novel gene mutated in Wiskott-Aldrich syndrome. Cell. 1994;78(4):635–44. Epub 1994/08/26. doi: 10.1016/0092-8674(94)90528-2 8069912.

86. Jinks RN, Puffenberger EG, Baple E, Harding B, Crino P, Fogo AB, et al. Recessive nephrocerebellar syndrome on the Galloway-Mowat syndrome spectrum is caused by homozygous protein-truncating mutations of WDR73. Brain. 2015;138(Pt 8):2173–90. doi: 10.1093/brain/awv153 26070982

87. Schaks M, Singh SP, Kage F, Thomason P, Klunemann T, Steffen A, et al. Distinct Interaction Sites of Rac GTPase with WAVE Regulatory Complex Have Non-redundant Functions in Vivo. Current biology: CB. 2018;28(22):3674–84 e6. doi: 10.1016/j.cub.2018.10.002 30393033

88. Yamazaki D, Fujiwara T, Suetsugu S, Takenawa T. A novel function of WAVE in lamellipodia: WAVE1 is required for stabilization of lamellipodial protrusions during cell spreading. Genes Cells. 2005;10(5):381–92. doi: 10.1111/j.1365-2443.2005.00845.x 15836768.

89. Bensenor LB, Kan HM, Wang N, Wallrabe H, Davidson LA, Cai Y, et al. IQGAP1 regulates cell motility by linking growth factor signaling to actin assembly. Journal of cell science. 2007;120(Pt 4):658–69. doi: 10.1242/jcs.03376 17264147.

90. Lorenz M, Yamaguchi H, Wang Y, Singer RH, Condeelis J. Imaging sites of N-wasp activity in lamellipodia and invadopodia of carcinoma cells. Current biology: CB. 2004;14(8):697–703. doi: 10.1016/j.cub.2004.04.008 15084285.

91. Tang H, Li A, Bi J, Veltman DM, Zech T, Spence HJ, et al. Loss of Scar/WAVE complex promotes N-WASP- and FAK-dependent invasion. Current biology: CB. 2013;23(2):107–17. doi: 10.1016/j.cub.2012.11.059 23273897.

92. Sarkar K, Sadhukhan S, Han SS, Vyas YM. Disruption of hSWI/SNF complexes in T cells by WAS mutations distinguishes X-linked thrombocytopenia from Wiskott-Aldrich syndrome. Blood. 2014;124(23):3409–19. doi: 10.1182/blood-2014-07-587642 25253772

93. Taylor MD, Sadhukhan S, Kottangada P, Ramgopal A, Sarkar K, D’Silva S, et al. Nuclear role of WASp in the pathogenesis of dysregulated TH1 immunity in human Wiskott-Aldrich syndrome. Sci Transl Med. 2010;2(37):37ra44. doi: 10.1126/scitranslmed.3000813 20574068

94. Juin A, Spence HJ, Martin KJ, McGhee E, Neilson M, Cutiongco MFA, et al. N-WASP Control of LPAR1 Trafficking Establishes Response to Self-Generated LPA Gradients to Promote Pancreatic Cancer Cell Metastasis. Developmental cell. 2019. doi: 10.1016/j.devcel.2019.09.018 31668663.

95. 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 Res. 2002;62(3):669–74. Epub 2002/02/07. 11830518.

96. Yamaguchi H, Lorenz M, Kempiak S, Sarmiento C, Coniglio S, Symons M, et al. Molecular mechanisms of invadopodium formation: the role of the N-WASP-Arp2/3 complex pathway and cofilin. The Journal of cell biology. 2005;168(3):441–52. Epub 2005/02/03. doi: 10.1083/jcb.200407076 15684033.

97. Innocenti M, Gerboth S, Rottner K, Lai FP, Hertzog M, Stradal TE, et al. Abi1 regulates the activity of N-WASP and WAVE in distinct actin-based processes. Nature cell biology. 2005;7(10):969–76. Epub 2005/09/13. doi: 10.1038/ncb1304 16155590.

98. Sarmiento C, Wang W, Dovas A, Yamaguchi H, Sidani M, El-Sibai M, et al. WASP family members and formin proteins coordinate regulation of cell protrusions in carcinoma cells. The Journal of cell biology. 2008;180(6):1245–60. Epub 2008/03/26. doi: 10.1083/jcb.200708123 18362183.

99. Coutts AS, Pires IM, Weston L, Buffa FM, Milani M, Li JL, et al. Hypoxia-driven cell motility reflects the interplay between JMY and HIF-1alpha. Oncogene. 2011;30(48):4835–42. doi: 10.1038/onc.2011.188 21625218.

100. Lai FP, Szczodrak M, Oelkers JM, Ladwein M, Acconcia F, Benesch S, et al. Cortactin Promotes Migration and PDGF-induced Actin Reorganization by Signaling to Rho-GTPases. Molecular biology of the cell. 2009. Epub 2009/05/22. doi: 10.1091/mbc.E08-12-1180 19458196.

101. Fukumi-Tominaga T, Mori Y, Matsuura A, Kaneko K, Matsui M, Ogata M, et al. DIP/WISH-deficient mice reveal Dia- and N-WASP-interacting protein as a regulator of cytoskeletal dynamics in embryonic fibroblasts. Genes Cells. 2009;14(10):1197–207. doi: 10.1111/j.1365-2443.2009.01345.x 19778379.

102. Meng W, Numazaki M, Takeuchi K, Uchibori Y, Ando-Akatsuka Y, Tominaga M, et al. DIP (mDia interacting protein) is a key molecule regulating Rho and Rac in a Src-dependent manner. EMBO J. 2004;23(4):760–71. doi: 10.1038/sj.emboj.7600095 14765113

103. Velle KB, Campellone KG. Enteropathogenic E. coli relies on collaboration between the formin mDia1 and the Arp2/3 complex for actin pedestal biogenesis and maintenance. PLoS pathogens. 2018;14(12):e1007485. doi: 10.1371/journal.ppat.1007485 30550556

104. Doolittle LK, Rosen MK, Padrick SB. Measurement and analysis of in vitro actin polymerization. Methods Mol Biol. 2013;1046:273–93. doi: 10.1007/978-1-62703-538-5_16 23868594


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