Dock10, a Cdc42 and Rac1 GEF, induces loss of elongation, filopodia, and ruffles in cervical cancer epithelial HeLa cells

被引:30
|
作者
Ruiz-Lafuente, Natalia [1 ]
Alcaraz-Garcia, Maria-Jose [1 ]
Garcia-Serna, Azahara-Maria [1 ]
Sebastian-Ruiz, Silvia [1 ]
Moya-Quiles, Maria-Rosa [1 ]
Garcia-Alonso, Ana-Maria [1 ]
Parrado, Antonio [1 ]
机构
[1] Virgen de la Arrixaca Clin Univ Hosp, Serv Immunol, Inst Biohlth Res IMIB Arrixaca, Murcia 30120, Spain
来源
BIOLOGY OPEN | 2015年 / 4卷 / 05期
关键词
Dock10; Dock9; Dock11; Cdc42; Rac1; filopodia; membrane ruffles; NUCLEOTIDE EXCHANGE FACTOR; MOUSE EMBRYONIC FIBROBLASTS; RHO GTPASES; GROWTH-FACTOR; DIRECTED MIGRATION; GENE-EXPRESSION; FAMILY GTPASES; B-LYMPHOCYTES; ACTIVATION; PROTEINS;
D O I
10.1242/bio.20149050
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Dock10 is one of the three members of the Dock-D family of Dock proteins, a class of guanine nucleotide exchange factors (GEFs) for Rho GTPases. Its homologs Dock9 and Dock11 are Cdc42 GEFs. Dock10 is required for maintenance of rounded morphology and amoeboid-type movement. Full-length isoforms of Dock10 have been recently cloned. Here, we address GTPase specificity and GEF activity of Dock10. In order of decreasing intensity, Dock10 interacted with nucleotide-free Rac1, Cdc42, and Rac3, and more weakly with Rac2, RhoF, and RhoG. Inducible expression of Dock10 in HeLa epithelial cells promoted GEF activity on Cdc42 and Rac1, and a morphologic change in two-dimensional culture consisting in loss of cell elongation, increase of filopodia, and ruffles. Area in contact with the substrate of cells that spread with non-elongated morphology was larger in cells expressing Dock10. Inducible expression of constitutively active mutants of Cdc42 and Rac1 in HeLa cells also induced loss of elongation. However, Cdc42 induced filopodia and contraction, and Rac1 induced membrane ruffles and flattening. When co-expressed with Dock10, Cdc42 potentiated filopodia, and Rac1 potentiated ruffles. These results suggest that Dock10 functions as a dual GEF for Cdc42 and Rac1, affecting cell morphology, spreading and actin cytoskeleton protrusions of adherent HeLa cells.
引用
收藏
页码:627 / 635
页数:9
相关论文
共 27 条
  • [1] DOCK9 induces membrane ruffles and Rac1 activity in cancer HeLa epithelial cells
    Ruiz-Lafuente, Natalia
    Minguela, Alfredo
    Parrado, Antonio
    [J]. BIOCHEMISTRY AND BIOPHYSICS REPORTS, 2018, 14 : 178 - 181
  • [2] The roles of Cdc42 and Rac1 in the formation of plasma membrane protrusions in cancer epithelial HeLa cells
    Natalia Ruiz-Lafuente
    Alfredo Minguela
    Manuel Muro
    Antonio Parrado
    [J]. Molecular Biology Reports, 2021, 48 : 4285 - 4294
  • [3] The roles of Cdc42 and Rac1 in the formation of plasma membrane protrusions in cancer epithelial HeLa cells
    Ruiz-Lafuente, Natalia
    Minguela, Alfredo
    Muro, Manuel
    Parrado, Antonio
    [J]. MOLECULAR BIOLOGY REPORTS, 2021, 48 (05) : 4285 - 4294
  • [4] Docetaxel induces Rac1 and Cdc42 Rho GTPase activation in prostate cancer cells
    Lopez Gonzalez, Andrea Paola
    Colon Gonzalez, Jessica
    Maria Fuentes, Maria C. Santa
    Dharmawardhane, Surangani
    Diaz Osterman, Carlos J.
    [J]. CANCER RESEARCH, 2024, 84 (06)
  • [5] Phosphorylation and activation of the Rac1 and Cdc42 GEF Asef in A431 cells stimulated by EGF
    Itoh, Reina E.
    Kiyokawa, Etsuko
    Aoki, Kazuhiro
    Nishioka, Teruko
    Akiyama, Tetsu
    Matsuda, Michiyuki
    [J]. JOURNAL OF CELL SCIENCE, 2008, 121 (16) : 2635 - 2642
  • [6] Cdc42/Rac1 participates in the control of telomerase activity in human nasopharyngeal cancer cells
    Yeh, YM
    Pan, YT
    Wang, TCV
    [J]. CANCER LETTERS, 2005, 218 (02) : 207 - 213
  • [7] Characterizing the listeriolysin O-induced activation of the Rho GTPases Rac1 and Cdc42 in epithelial cells.
    Lam, J.
    Vadia, S.
    Seveau, S. M.
    [J]. MOLECULAR BIOLOGY OF THE CELL, 2015, 26
  • [8] IQGAP1 activates Tcf signal independent of Rac1 and Cdc42 in injury and repair of bronchial epithelial cells
    Wang, Yongping
    Wang, Aifeng
    Wang, Fang
    Wang, Mangxiang
    Zhu, Min
    Ma, Yan
    Wu, Renliang
    [J]. EXPERIMENTAL AND MOLECULAR PATHOLOGY, 2008, 85 (02) : 122 - 128
  • [9] IBP regulates epithelial-to-mesenchymal transition and the motility of breast cancer cells via Rac1, RhoA and Cdc42 signaling pathways
    Z Zhang
    M Yang
    R Chen
    W Su
    P Li
    S Chen
    Z Chen
    A Chen
    S Li
    C Hu
    [J]. Oncogene, 2014, 33 : 3374 - 3382
  • [10] IBP regulates epithelial-to-mesenchymal transition and the motility of breast cancer cells via Rac1, RhoA and Cdc42 signaling pathways
    Zhang, Z.
    Yang, M.
    Chen, R.
    Su, W.
    Li, P.
    Chen, S.
    Chen, Z.
    Chen, A.
    Li, S.
    Hu, C.
    [J]. ONCOGENE, 2014, 33 (26) : 3374 - 3382