A Dictyostelium homologue of WASP is required for polarized F-actin assembly during chemotaxis.
The actin cytoskeleton controls the overall structure of cells and is highly polarized in chemotaxing cells, with F-actin assembled predominantly in the anterior leading edge and to a lesser degree in the cell's posterior. Wiskott-Aldrich syndrome protein (WASP) has emerged as a central player in controlling actin polymerization. We have investigated WASP function and its regulation in chemotaxing Dictyostelium cells and demonstrated the specific and essential role of WASP in organizing polarized F-actin assembly in chemotaxing cells. Cells expressing very low levels of WASP show reduced F-actin levels and significant defects in polarized F-actin assembly, resulting in an inability to establish axial polarity during chemotaxis. GFP-WASP preferentially localizes at the leading edge and uropod of chemotaxing cells and the B domain of WASP is required for the localization of WASP. We demonstrated that the B domain binds to PI(4,5)P2 and PI(3,4,5)P3 with similar affinities. The interaction between the B domain and PI(3,4,5)P3 plays an important role for the localization of WASP to the leading edge in chemotaxing cells. Our results suggest that the spatial and temporal control of WASP localization and activation is essential for the regulation of directional motility.
Myers
Scott A
SA
Department of Pharmacology, Vanderbilt University Medical Center, Nashville TN 37232-6600, USA.
Han
Ji W
JW
Lee
Yoonsung
Y
Firtel
Richard A
RA
Chung
Chang Y
CY
D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D016764:Cell Polarity; D002633:Chemotaxis / Q000502:physiology*; D004023:Dictyostelium / Q000166:cytology / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D010716:Phosphatidylinositols / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D051316:Wiskott-Aldrich Syndrome Protein
D000199:Actins; D010716:Phosphatidylinositols; D011506:Proteins; D015800:Protozoan Proteins; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein
Semin Hematol. 1998 Oct;35(4):332-45
9801262
Genes Dev. 1998 Nov 15;12(22):3564-78
9832508
Curr Biol. 1998 Dec 17-31;8(25):1347-56
9889097
EMBO J. 1999 Feb 1;18(3):501-11
9927410
Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3739-44
10097107
EMBO J. 1999 Apr 15;18(8):2092-105
10205164
Cell. 1999 Apr 16;97(2):221-31
10219243
Science. 1999 Apr 30;284(5415):765-70
10221901
Curr Opin Cell Biol. 2000 Feb;12(1):104-12
10679366
Semin Cell Dev Biol. 1999 Dec;10(6):609-19
10706825
Nature. 2000 Mar 9;404(6774):151-8
10724160
Bioessays. 2000 Jul;22(7):603-15
10878573
Curr Opin Genet Dev. 2000 Aug;10(4):421-7
10889066
Gene. 2000 Jul 11;252(1-2):71-82
10903439
J Cell Biol. 2000 Sep 18;150(6):1299-310
10995436
J Cell Biol. 2000 Sep 18;150(6):1311-20
10995437
J Cell Biol. 2000 Sep 18;150(6):F117-20
10995455
Trends Cell Biol. 2000 Nov;10(11):466-73
11050418
Science. 2000 Oct 27;290(5492):801-6
11052943
Nat Cell Biol. 2001 Jan;3(1):76-82
11146629
Immunol Rev. 2000 Dec;178:118-28
11213796
Genes Cells. 2001 Mar;6(3):225-35
11260266
J Cell Biol. 2001 May 14;153(4):795-810
11352940
Mol Cell. 2001 May;7(5):937-47
11389841
Blood. 2001 Aug 15;98(4):1086-94
11493455
Dev Cell. 2001 Dec;1(6):743-7
11740936
Curr Biol. 2001 Dec 11;11(24):1903-13
11747816
J Cell Biol. 2002 Feb 18;156(4):689-701
11854309
Cell. 2002 May 31;109(5):611-23
12062104
Nat Cell Biol. 2002 Jul;4(7):513-8
12080345
Clin Immunol. 1999 Aug;92(2):128-37
10444357
Trends Cell Biol. 1999 Sep;9(9):345-50
10461187
Pediatrics. 1954 Feb;13(2):133-9
13133561
J Cell Biol. 1999 Nov 1;147(3):559-76
10545500
Annu Rev Cell Dev Biol. 1999;15:469-517
10611970
Science. 2000 Feb 11;287(5455):1037-40
10669415
Cell. 1994 Aug 26;78(4):635-44
8069912
Curr Biol. 1995 Nov 1;5(11):1280-5
8574585
Cell. 1996 Mar 8;84(5):723-34
8625410
J Muscle Res Cell Motil. 1996 Apr;17(2):269-74
8793728
EMBO J. 1996 Oct 1;15(19):5326-35
8895577
J Cell Biol. 1997 Feb 10;136(3):649-58
9024694
Curr Biol. 1997 Mar 1;7(3):176-83
9276758
J Immunol. 1997 May 1;158(9):4021-5
9126958
J Cell Biol. 1997 Jul 28;138(2):363-74
9230078
Science. 1998 Jan 23;279(5350):509-14
9438836
Cell Motil Cytoskeleton. 1998;39(1):31-51
9453712
Curr Biol. 1998 Mar 26;8(7):405-8
9545201
Springer Semin Immunopathol. 1998;19(4):435-58
9618767
J Neuroimmunol. 1998 May 1;85(1):33-43
9626995
J Immunol. 1998 Jul 15;161(2):1026-33
9670984
Br J Haematol. 1998 Jun;101(4):659-65
9674738
Immunity. 1998 Jul;9(1):81-91
9697838
J Cell Biol. 1998 Sep 7;142(5):1325-35
9732292
Cell. 1998 Oct 2;95(1):81-91
9778249
J Biol Chem. 2002 Oct 4;277(40):37771-6
12147689
Mol Biol Cell. 2002 Nov;13(11):4045-59
12429845
Immunol Rev. 2003 Apr;192:98-112
12670398
J Biol Chem. 2003 Jun 6;278(23):20445-8
12672811
Curr Biol. 2003 Jun 17;13(12):1000-8
12814545
J Cell Sci. 2003 Sep 1;116(Pt 17):3471-8
12893811
Nat Cell Biol. 2004 May;6(5):420-6
15107862
Cell. 2004 Jul 23;118(2):203-16
15260990
Cancer Res. 1970 Jun;30(6):1632-44
4318696
J Clin Invest. 1974 Aug;54(2):486-93
4136226
Gan. 1979 Aug;70(4):559-61
510854
J Cell Biol. 1982 Mar;92(3):807-21
6282894
Mol Cell Biol. 1987 Jan;7(1):149-59
3031453
J Biol Chem. 1990 Jun 5;265(16):9236-40
2345173
Curr Opin Immunol. 1994 Feb;6(1):113-24
8172673
Mol Biol Cell. 1999 May;10(5):1309-23
10233146
FEBS Lett. 1999 May 28;451(3):220-6
10371193