Zyxin-mediated actin assembly is required for efficient wound closure.
Cytoskeletal regulation of cell adhesion is vital to the organization of multicellular structures. The focal adhesion protein zyxin emerged as a key regulator of actin assembly because zyxin recruits Enabled/vasodilator-stimulated phospho-proteins (Ena/VASP) to promote actin assembly. Zyxin also localizes to the sites of cell-cell adhesion and is thought to promote actin assembly with Ena/VASP. Using shRNA targeted to zyxin, we analyzed the roles of zyxin at adhesive contacts. In zyxin-deficient cells, the actin assembly at both focal adhesion and cell-cell adhesion was limited, but their migration rate was unchanged. Cell spreading on E-cadherin-coated surfaces and the formation of cell clusters were slower for zyxin-deficient cells than wild type cells. By ablating a single cell within a cell monolayer, we quantified the rate of wound closure driven by a contractile circumferential actin ring. Zyxin-deficient cells failed to recruit VASP to cell-cell junctions at the wound edge and had a slower wound closure rate than wild type cells. Our results suggest that, by recruiting VASP, zyxin regulates actin assembly at the sites of force-bearing cell-cell adhesion.
Nguyen
Thuc Nghi
TN
Biomedical Engineering Department, University of California, Davis, California 95616, USA.
Uemura
Arisa
A
Shih
Wenting
W
Yamada
Soichiro
S
D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology; D002450:Cell Communication / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004285:Dogs; D022001:Focal Adhesions / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007365:Intercellular Junctions / Q000378:metabolism; D018613:Microscopy, Confocal; D034622:RNA Interference
D000199:Actins; D015820:Cadherins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C092744:ENA-VASP proteins; D049452:Green Fluorescent Proteins
Cell. 2000 Jan 21;100(2):209-19
10660044
Mol Biol Cell. 2001 Oct;12(10):3103-13
11598195
J Cell Sci. 2007 Nov 1;120(Pt 21):3870-82
17940061
J Cell Sci. 2009 Jun 15;122(Pt 12):1947-53
19494122
Nat Cell Biol. 2001 May;3(5):E117-23
11331897
Mol Cell Biol. 2003 Jan;23(1):70-9
12482962
Nat Cell Biol. 2004 Jan;6(1):21-30
14647292
J Biol Chem. 2004 Aug 6;279(32):34062-70
15159390
Science. 2007 Feb 16;315(5814):992-5
17303755
J Biol Chem. 1991 Mar 25;266(9):5847-53
2005121
Nat Cell Biol. 2008 Sep;10(9):1039-50
19160484
J Biol Chem. 2000 Jul 21;275(29):22503-11
10801818
Nature. 1999 Oct 7;401(6753):613-6
10524632
FEBS Lett. 1996 Dec 9;399(1-2):103-7
8980130
J Cell Biol. 2007 Nov 19;179(4):761-75
17998398
J Biol Chem. 2006 Jun 9;281(23):16178-88
16613855
Curr Biol. 2002 Mar 5;12(5):379-82
11882288
J Cell Biol. 2006 Feb 27;172(5):771-82
16505170
J Cell Biol. 2005 Oct 24;171(2):209-15
16247023
Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7956-60
7644520
Exp Cell Res. 2007 Nov 15;313(19):4025-40
17765222
J Cell Sci. 2009 May 15;122(Pt 10):1665-79
19401336
J Cell Biol. 2007 Jul 30;178(3):517-27
17646397
J Cell Sci. 2008 Sep 1;121(Pt 17):2795-804
18682496
Bioessays. 1997 Nov;19(11):949-57
9394617
J Biol Chem. 2008 Apr 11;283(15):9814-9
18283104
Nat Cell Biol. 2001 Aug;3(8):699-707
11483954
J Cell Sci. 1998 Nov;111 ( Pt 22):3323-32
9788874
Biochem J. 1996 Sep 15;318 ( Pt 3):753-7
8836115
Mol Biol Cell. 2006 Mar;17(3):1085-95
16371509
Nat Cell Biol. 2010 Jun;12(6):533-42
20453849
Cell. 2002 May 17;109(4):509-21
12086607
EMBO J. 2001 Oct 15;20(20):5603-14
11598004
Cell. 2005 Dec 2;123(5):889-901
16325582
Nature. 2008 Jun 5;453(7196):751-6
18480755
J Cell Biol. 1993 May;121(3):565-78
8486737
J Cell Biol. 1992 Mar;116(6):1381-93
1541635
J Biol Chem. 2001 Sep 14;276(37):34759-67
11395501
Mol Biol Cell. 2000 Jan;11(1):117-29
10637295