Sra-1 and Nap1 link Rac to actin assembly driving lamellipodia formation

被引:306
作者
Steffen, A
Rottner, K
Ehinger, J
Innocenti, M
Scita, G
Wehland, J
Stradal, TEB
机构
[1] German Res Ctr Biotechnol, Dept Cell Biol, D-38124 Braunschweig, Germany
[2] European Inst Oncol, Dept Expt Oncol, Milan, Italy
关键词
Abi; lamellipodium; Rac; WAVE;
D O I
10.1038/sj.emboj.7600084
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The Rho-GTPase Rac1 stimulates actin remodelling at the cell periphery by relaying signals to Scar/WAVE proteins leading to activation of Arp2/3-mediated actin polymerization. Scar/WAVE proteins do not interact with Rac1 directly, but instead assemble into multiprotein complexes, which was shown to regulate their activity in vitro. However, little information is available on how these complexes function in vivo. Here we show that the specifically Rac1-associated protein-1 (Sra-1) and Nck-associated protein 1 (Nap1) interact with WAVE2 and Abi-1 (e3B1) in resting cells or upon Rac activation. Consistently, Sra-1, Nap1, WAVE2 and Abi-1 translocated to the tips of membrane protrusions after microinjection of constitutively active Rac. Moreover, removal of Sra-1 or Nap1 by RNA interference abrogated the formation of Rac-dependent lamellipodia induced by growth factor stimulation or aluminium fluoride treatment. Finally, microinjection of an activated Rac failed to restore lamellipodia protrusion in cells lacking either protein. Thus, Sra-1 and Nap1 are constitutive and essential components of a WAVE2- and Abi-1-containing complex linking Rac to site-directed actin assembly.
引用
收藏
页码:749 / 759
页数:11
相关论文
共 40 条
  • [31] CYFIP/Sra-1 controls neuronal connectivity in Drosophila and links the Rac1 GTPase pathway to the fragile X protein
    Schenck, A
    Bardoni, B
    Langmann, C
    Harden, N
    Mandel, JL
    Giangrande, A
    [J]. NEURON, 2003, 38 (06) : 887 - 898
  • [32] EPS8 and E3B1 transduce signals from Ras to Rac
    Scita, G
    Nordstrom, J
    Carbone, R
    Tenca, P
    Giardina, G
    Gutkind, S
    Bjarnegärd, M
    Betsholtz, C
    Di Fiore, PP
    [J]. NATURE, 1999, 401 (6750) : 290 - 293
  • [33] Genomic organization and expression profile of the human and mouse WAVE gene family
    Sossey-Alaoui, K
    Head, K
    Nowak, N
    Cowell, JK
    [J]. MAMMALIAN GENOME, 2003, 14 (05) : 314 - 322
  • [34] The GEX-2 and GEX-3 proteins are required for tissue morphogenesis and cell migrations in C-elegans
    Soto, MC
    Qadota, H
    Kasuya, K
    Inoue, M
    Tsuboi, D
    Mello, CC
    Kaibuchi, K
    [J]. GENES & DEVELOPMENT, 2002, 16 (05) : 620 - 632
  • [35] The Abl interactor proteins localize to sites of actin polymerization at the tips of lamellipodia and filopodia
    Stradal, T
    Courtney, KD
    Rottner, K
    Hahne, P
    Small, JV
    Pendergast, AM
    [J]. CURRENT BIOLOGY, 2001, 11 (11) : 891 - 895
  • [36] A RAT MONOCLONAL-ANTIBODY REACTING SPECIFICALLY WITH THE TYROSYLATED FORM OF ALPHA-TUBULIN .1. BIOCHEMICAL-CHARACTERIZATION, EFFECTS ON MICROTUBULE POLYMERIZATION INVITRO, AND MICROTUBULE POLYMERIZATION AND ORGANIZATION INVIVO
    WEHLAND, J
    WILLINGHAM, MC
    SANDOVAL, IV
    [J]. JOURNAL OF CELL BIOLOGY, 1983, 97 (05) : 1467 - 1475
  • [37] In mouse brain profilin I and profilin II associate with regulators of the endocytic pathway and actin assembly
    Witke, W
    Podtelejnikov, AV
    Di Nardo, A
    Sutherland, JD
    Gurniak, CB
    Dotti, C
    Mann, M
    [J]. EMBO JOURNAL, 1998, 17 (04) : 967 - 976
  • [38] Isolation of hNap1BP which interacts with human Nap1 (NCKAP1) whose expression is down-regulated in Alzheimer's disease
    Yamamoto, A
    Suzuki, T
    Sakaki, Y
    [J]. GENE, 2001, 271 (02) : 159 - 169
  • [39] WAVE2 is required for directed cell migration and cardiovascular development
    Yamazaki, D
    Suetsugu, S
    Miki, H
    Kataoka, Y
    Nishikawa, SI
    Fujiwara, T
    Yoshida, N
    Takenawa, T
    [J]. NATURE, 2003, 424 (6947) : 452 - 456
  • [40] WAVE2 deficiency reveals distinct roles in embryogenesis and Rac-mediated actin-based motility
    Yan, C
    Martinez-Quiles, N
    Eden, S
    Shibata, T
    Takeshima, F
    Shinkura, R
    Fujiwara, Y
    Bronson, R
    Snapper, SB
    Kirschner, MW
    Geha, R
    Rosen, FS
    Alt, FW
    [J]. EMBO JOURNAL, 2003, 22 (14) : 3602 - 3612