MISP regulates the IQGAP1/Cdc42 complex to collectively orchestrate spindle orientation and mitotic progression

被引:0
作者
Barbara Vodicska
Berati Cerikan
Elmar Schiebel
Ingrid Hoffmann
机构
[1] German Cancer Research Center,Cell Cycle Control and Carcinogenesis, F045
[2] DKFZ,undefined
[3] Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH),undefined
[4] DKFZ – ZMBH Alliance,undefined
[5] Im Neuenheimer Feld 282,undefined
[6] Heidelberg University,undefined
来源
Scientific Reports | / 8卷
关键词
D O I
暂无
中图分类号
学科分类号
摘要
Precise mitotic spindle orientation is essential for both cell fate and tissue organization while defects in this process are associated with tumorigenesis and other diseases. In most animal cell types, the dynein motor complex is anchored at the cell cortex and exerts pulling forces on astral microtubules to position the spindle. The actin-binding protein MISP controls spindle orientation and mitotic progression in human cells. However, the exact underlying mechanism remains to be elucidated. Here we report that MISP interacts with the multidomain scaffolding protein IQGAP1. We further show that MISP binds to the active form of Cdc42 through IQGAP1. Depletion of MISP promotes increased accumulation of IQGAP1 at the cell cortex and a decrease in its Cdc42-binding capacity leading to reduced active Cdc42 levels. Interestingly, overexpression of IQGAP1 can rescue mitotic defects caused by MISP downregulation including spindle misorientation, loss of astral microtubules and prolonged mitosis and also restores active Cdc42 levels. Importantly, we find that IQGAP1 acts downsteam of MISP in regulating astral microtubule dynamics and the localization of the dynactin subunit p150glued that is crucial for proper spindle positioning. We propose that MISP regulates IQGAP1 and Cdc42 to ensure proper mitotic progression and correct spindle orientation.
引用
收藏
相关论文
共 50 条
  • [41] JAM-A regulates cortical dynein localization through Cdc42 to control planar spindle orientation during mitosis
    Tuncay, Hueseyin
    Brinkmann, Benjamin F.
    Steinbacher, Tim
    Schuermann, Annika
    Gerke, Volker
    Iden, Sandra
    Ebnet, Klaus
    [J]. NATURE COMMUNICATIONS, 2015, 6
  • [42] JAM-A regulates cortical dynein localization through Cdc42 to control planar spindle orientation during mitosis
    Hüseyin Tuncay
    Benjamin F. Brinkmann
    Tim Steinbacher
    Annika Schürmann
    Volker Gerke
    Sandra Iden
    Klaus Ebnet
    [J]. Nature Communications, 6
  • [44] Role of IQGAP1, a target of the small GTPases Cdc42 and Rac1, in regulation of E-cadherin-mediated cell-cell adhesion
    Kuroda, S
    Fukata, M
    Nakagawa, M
    Fujii, K
    Nakamura, T
    Ookubo, T
    Izawa, I
    Nagase, T
    Nomura, N
    Tani, H
    Shoji, I
    Matsuura, Y
    Yonehara, S
    Kaibuchi, K
    [J]. SCIENCE, 1998, 281 (5378) : 832 - 835
  • [45] Hyaluronan-CD44 interaction with IQGAP1 promotes Cdc42 and ERK signaling, leading to actin binding, Elk-1/estrogen receptor transcriptional activation, and ovarian cancer progression
    Bourguignon, LYW
    Gilad, E
    Rothman, K
    Peyrollier, K
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (12) : 11961 - 11972
  • [46] 基底细胞样型乳腺癌中Cdc42和IQGAP1的表达及临床意义
    陈小悦
    张金库
    陈雪
    赵文明
    陈红
    孙吉瑞
    李金梅
    [J]. 肿瘤学杂志, 2015, 21 (05) : 387 - 391
  • [47] Human mitotic spindle-associated protein PRC1 inhibits MgcRacGAP activity toward Cdc42 during the metaphase
    Ban, R
    Irino, Y
    Fukami, K
    Tanaka, H
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (16) : 16394 - 16402
  • [48] N-3-oxo-dodecanoyl-L-homoserine lactone inhibits epithelial cells migration via Rac1/Cdc42, IQGAP1 and actin remodeling
    Yakymenko, L.
    Turkina, M.
    Karlsson, T.
    Magnusson, K-E.
    Vikstrom, E.
    [J]. MOLECULAR BIOLOGY OF THE CELL, 2011, 22
  • [49] Interactions Among IQGAP1, Cdc42/Rac1, N-WASP and Actin Quantified by In vitro Reconstitution and Live Cell, Three-Color FRET Microscopy
    Wallrabe, H.
    Cai, Y.
    Sun, Y.
    Periasamy, A.
    Luzes, R.
    Fang, X.
    Kan, H-M.
    Cameron, L. C.
    Schafer, D. A.
    Bloom, G. S.
    [J]. MOLECULAR BIOLOGY OF THE CELL, 2011, 22
  • [50] A Rich1/Amot complex regulates the Cdc42 GTPase and apical-polarity proteins in epithelial cells
    Wells, Clark D.
    Fawcett, James P.
    Traweger, Andreas
    Yamanaka, Yojiro
    Goudreault, Marilyn
    Elder, Kelly
    Kulkarni, Sarang
    Gish, Gerald
    Virag, Cristina
    Lim, Caesar
    Colwill, Karen
    Starostine, Andrei
    Metalnikov, Pavel
    Pawson, Tony
    [J]. CELL, 2006, 125 (03) : 535 - 548