Académique Documents
Professionnel Documents
Culture Documents
Review
a r t i c l e
i n f o
Article history:
Received 21 January 2010
Received in revised form 12 April 2010
Accepted 14 April 2010
Available online 20 April 2010
Keywords:
Actin cytoskeleton
Cell cycle
Mitosis
Rho GTPases
Focal adhesion
a b s t r a c t
The network of actin laments is one of the crucial cytoskeletal structures contributing to the morphological framework of a cell and which participates in the dynamic regulation of cellular functions. In
adherent cell types, cells adhere to the substratum during interphase and spread to assume their characteristic shape supported by the actin cytoskeleton. This actin cytoskeleton is reorganized during mitosis
to form rounded cells with increased cortical rigidity. The actin cytoskeleton is re-established after mitosis, allowing cells to regain their extended shape and attachment to the substratum. The modulation of
such drastic changes in cell shape in coordination with cell cycle progression suggests a tight regulatory
interaction between cytoskeleton signalling, cellcell/cellmatrix adhesions and mitotic events. Here,
we review the contribution of the actin cytoskeleton to cell cycle progression with an emphasis on the
effectors responsible for the regulation of the actin cytoskeleton and integration of their activities with
the cell cycle machinery.
2010 Elsevier Ltd. All rights reserved.
Contents
1.
2.
3.
4.
5.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1622
Actin cytoskeleton, myosin and the cell cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1623
2.1.
Actin cytoskeleton in cell cycle control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1623
2.2.
Actin, myosin and the regulation of the mitotic spindle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1623
2.3.
Septin, actin cytoskeleton, and the cell cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1627
Rho GTPases, their regulators and the cell cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1627
3.1.
RhoA and partners in cytokinesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1627
3.2.
RhoA and partners in other stages of mitosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1628
3.3.
Cdc42 and partners . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1629
3.4.
Cyclin-dependent kinase and Rho GTPases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1629
Cell attachment and the cell cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1629
4.1.
Integrin signalling and the cell cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1630
4.2.
Cadherin signalling and the cell cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1630
4.3.
Focal adhesion proteins and the cell cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1630
Conclusion and perspective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1631
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1631
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1631
1. Introduction
Y.-W. Heng, C.-G. Koh / The International Journal of Biochemistry & Cell Biology 42 (2010) 16221633
1623
1624
Y.-W. Heng, C.-G. Koh / The International Journal of Biochemistry & Cell Biology 42 (2010) 16221633
Fig. 1. Different localization of proteins at interphase and mitosis. HeLa cells were harvested at different stages of the cell cycle and immunostained with (A) Top panels:
anti--tubulin antibodies. Bottom panels: phalloidin for F-actin. (B) Non-muscle myosin II heavy chain antibodies (red), DAPI (blue). (C) Top panels: anti-phospho LIMK1
(T508)/LIMK2 (T505) antibodies (green). Bottom panels: Merged image with anti--tubulin (red) and DAPI stain (blue). (D) Top panels: anti-phospho PAK1 (T423) antibodies
(red). Bottom panels: merged image with anti--tubulin (green) and DAPI (blue). All bars: 10 m.
Y.-W. Heng, C.-G. Koh / The International Journal of Biochemistry & Cell Biology 42 (2010) 16221633
1625
Table 1
Summary of different reagents used to perturb the actin cytoskeleton and their effects on cell cycle progression.
Drug
Target
Action
Phenotype(s) reported
Reference(s)
G2 arrest
Clostridium botulinum
exoenzyme C3 transferase
ROCK I, ROCK II
Y-27632-Rock inhibitor
ML-7, ML-9
MLCK
2,3-Butanedione monoxime
(BDM)
Blebbistatin
Myosin
Calyculin A
Protein phosphatases
CEP1347
WR-PAK18
PAK1
Cytochalasin D
Actin
Latrunculin A/B
Actin
Jasplakinolide
Actin
Myosin II
G1 arrest, inhibits
kinetochore-microtubule elongation
Failure in centrosome separation
Cytokinesis defect
Nheu
et
al.
(2004)
Gachet et al. (2001), Lee and Song
(2007), Forer et al. (2007)
1626
Y.-W. Heng, C.-G. Koh / The International Journal of Biochemistry & Cell Biology 42 (2010) 16221633
Table 2
Summary of the role of different groups of proteins in actin cytoskeleton regulation and cell cycle progression.
Protein Group
Protein
Reference(s)
Myosin II
Myosin X
Anillin
Cortactin
Moesin
Septin
RhoA
Rac1
Lamellapodia formation.
G1 -S transition; cytokinesis.
Cdc42
Filopodia formation.
p190RhoGAP
Ect2
RhoA GAP.
RhoA GEF, Cdc42 GEF during
mitosis.
G1 -S transition;
kinetochore-microtubule stabilization;
spindle biorientation; metaphase
chromosome alignment; cytokinesis.
Mitotic cell rounding.
Contractile ring formation; contraction
of contractile ring at cleavage furrow.
GEF-H1
Actin binding
Rho GTPase
MgcRacGAP
Lfc
MyoGEF
RhoA GEF.
RhoA GEF; myosin II binding.
ROCK
LIMK1
LIMK2
Colin
mDia1
PRK2/PKN2
PAK1
N-WASP
the maintenance of cell shape and rigidity is sufcient to stabilize the mitotic spindles. Moesins function in rounding up of cells
appears to be independent of myosin II because cells expressing
active T559D moesin but lacking myosin light chain are still able
to round up during mitosis (Kunda et al., 2008). However, it is
very likely that both moesin-actin and myosin-actin activities are
required to establish the rounded cell shape and rigidity for proper
spindle assembly and positioning.
Actin and myosin structures also participate in generating
the forces required for chromosome segregation. Treatment of
crane-y spermatocytes with actin depolymerization drugs such
as cytochalasin D and lantrunculin A or myosin ATPase inhibitors
like butanedione monoxime (BDM) causes inhibition of spindle
microtubule elongation (Forer et al., 2007). Conversely, nonspecic inhibition of myosin light chain phosphatase by calyculin A
Y.-W. Heng, C.-G. Koh / The International Journal of Biochemistry & Cell Biology 42 (2010) 16221633
1627
Table 3
The localization of different proteins linked to the actin cytoskeleton in interphase and mitosis.
Protein
F-actin
Myosin II
Anillin
Septin
Cortactin
Ect2
GEF-H1
LIMK1
LIMK2
MyoGEF
PAK1
RhoA
HEF1
Integrin-linked kinase (ILK)
Focal adhesion kinase (FAK)
Pyk2
Paxillin
Zyxin
M-phase
Contractile ring
Contractile ring
Contractile ring
Contractile ring
Centrosomes (phosphorylated from)
Central spindle
Mitotic spindle; midzone
Centrosomes; equatorial cortex; contractile ring
Mitotic spindle, contractile ring
Central spindle
Centrosomes; contractile ring; mid-body
Contractile ring
Mitotic spindle; mid-body
Centrosomes
Centrosones
Centrosomes
Centrosomes
Mitotic spindle; central spindle
Reference(s)
Schroeder (1968)
Mabuchi and Okuno (1977)
Piekny and Glotzer (2008)
Joo et al. (2007)
Wang et al. (2008)
Nishimura and Yonemura (2006)
Birkenfeld et al. (2007)
Sumi et al. (2006)
Sumi et al. (2006)
Asiedu et al. (2009)
Zhao et al. (2005)
Yuce et al. (2005)
Law et al. (1998)
Fielding et al. (2008)
Rodriguez-Fernandez et al. (1999)
Rodriguez-Fernandez et al. (1999)
Herreros et al. (2000)
Hirota et al. (2000)
1628
Y.-W. Heng, C.-G. Koh / The International Journal of Biochemistry & Cell Biology 42 (2010) 16221633
Fig. 2. Functional connections between proteins involved in the regulation of Rho GTPases, the actin cytoskeleton and cell cycle progression. The activities of different
proteins and how they can inuence one another at different phases of the cell cycle are summarized.
regulate only spindle assembly, has been found to also control the
localization of ECT2 to the central spindle and RhoA at the equator
in anaphase (Brennan et al., 2007; Burkard et al., 2007; Petronczki et
al., 2007). Inhibition of Plk1 blocks the interaction of ECT2 with the
midzone anchor HsCyk4 and the assembly of the contractile ring,
resulting in the inhibition of cytokinesis and the formation of binucleate cells. Recently, centrosome/spindle pole-associated protein
(CSPP) has been found to target MyoGEF (Myosin II-interacting GEF)
to the central spindle during anaphase. MyoGEF also interacts with
ECT2. Knockdown of MyoGEF results in mislocalization of ECT2
and RhoA during cytokinesis (Asiedu et al., 2009). Centralspindlin
which is localized to both the central spindle microtubules and the
tips of astral microtubules near the equatorial cortex is reported
to recruit ECT2 to the central spindle (Nishimura and Yonemura,
2006). Knockdown of centralspindlin component, MKLP1, causes
failure of ECT2 to localize to the equatorial cell cortex (Yuce et al.,
2005).
Another Rho GTPase regulator which participates in the control of cytokinesis and contractile ring assembly is MgcRacGAP
(also known as HsCyk4). MgcRacGAP is a GTPase-activating protein for Rac and Cdc42 but is converted to a GAP for RhoA when
phophorylated by Aurora-B in M phase of the cell cycle (Minoshima
et al., 2003). Silencing of MgcRacGAP by RNAi results in the loss of
ingression of the cleavage furrow and hence failure of the cells to
undergo cytokinesis (Zhao and Fang, 2005). MgcRacGAP interacts
with ECT2 and therefore may exert its effect via ECT2. A more recent
report proposes a model where the GAP activities of MgcRacGAP
and GEF activity of ECT2 act concurrently to promote a ux of RhoA
Y.-W. Heng, C.-G. Koh / The International Journal of Biochemistry & Cell Biology 42 (2010) 16221633
1629
of the centrosome in the late G2 phase. PAK1 activity may also play
an important role in the regulation of astral microtubule dynamics during mitosis since over-expression of active PAK1 resulted in
multiple spindle orientations (Vadlamudi et al., 2000).
Studies have also linked PAK1 signalling to G1 to S phase transition via the regulation of the cyclin D1 machinery. It has been shown
that in Ras transformed NIH 3T3 cells, the addition of two distinct
and specic PAK1-3 inhibitors, CEP-1347 and WR-PAK18 was able
to block malignant growth by down-regulation of cyclin D1 (Nheu
et al., 2004). Consistent with this, perturbation of PAK1 activity by
PAK1-KID, or knockdown of PAK1 by siRNA resulted in a marked
decrease in cyclin D1 expression (Balasenthil et al., 2004). So far,
a direct linkage of Cdc42 or Rac1 activity to these activities of PAK
has not been documented, even though a concomitant increase in
Cdc42 and PAK1 activity has been reported (Oceguera-Yanez et al.,
2005). Thus PAK1 may exhibit its function in a GTPase-dependent
or independent pathway.
Two recent papers have illustrated that Cdc42 is important in
controlling spindle orientation in mitotic cells (Jaffe et al., 2008;
Mitsushima et al., 2009). Deletion of Cdc42 did not affect cell polarity but instead caused mis-orientation of the spindle leading to
inappropriate positioning of the apical surfaces after cell division
(Jaffe et al., 2008). Mitsushima et al. (2009) went further to demonstrate that two independent pathways downstream of Cdc42 are
involved in regulating spindle orientation: one involving Cdc42PAK2-PIX and the other involving phosphatidylinositol 3 kinase
(PI3K). It appears that the two independent pathways collectively
affect the phosphatidyl 3,4,5 triphosphate (PIP3) levels and the
cortical actin structures (Mitsushima et al., 2009).
Not much has been reported about Rac1 and its role in the control of the cell cycle. One recent report suggests that the inhibition
of Rac by the CYK-4/MgcRacGAP of the centralspindlin complex is
essential for cytokinesis in C. elegans (Canman et al., 2008). Depletion of Rac but not RhoA can rescue the cytokinesis defect of a CYK-4
GAP mutant. This work suggests a parallel inhibition of Rac and activation of RhoA during cytokinesis, most probably to prevent the
activation of Arp2/3 complex by WASP or WAVE which is downstream of Rac. The net result is the prevention of the formation of
other actin networks which may interfere with the contractile ring.
3.4. Cyclin-dependent kinase and Rho GTPases
That the onset of mitosis requires activation of CDK1 and is
accompanied by drastic rearrangement of the actin cytoskeleton
leading to the rounding up of the cell, suggests an intimate regulatory connection between CDK1 and actin cytoskeleton. While
the exact signalling pathways of CDK1 activity leading to mitotic
cytoskeletal changes remain poorly understood, p190 Rho GTPaseactivating protein (GAP) has been proposed as a major downstream
effector of CDK1 (Maddox and Burridge, 2003). Activated CDK1
phosphorylates p190RhoGAP, down regulating its activity and thus
decreases GTP hydrolysis by RhoA. This triggers a signalling cascade
through ROCK and MLC phosphatase, that regulates cytoskeleton
rearrangement observed in mitosis (Amano et al., 1996; Maddox
and Burridge, 2003).
4. Cell attachment and the cell cycle
Attachment of cells to the extracellular matrix (ECM) or other
cells has long been implicated in cell cycle regulation. During cell
division, the cells undergo extensive cell shape changes to detach
from and reattach to the ECM. While cellmatrix adhesions have
been reported to reduce during mitosis, cellcell adhesions via the
desmosomes, tight junctions and zonulae adherentes in epithelial
cells are maintained throughout cell divisions (Baker and Garrod,
1630
Y.-W. Heng, C.-G. Koh / The International Journal of Biochemistry & Cell Biology 42 (2010) 16221633
Y.-W. Heng, C.-G. Koh / The International Journal of Biochemistry & Cell Biology 42 (2010) 16221633
one set of events is completed before the next phase of the cell cycle
is initiated.
FAK serves as an important signalling protein at focal adhesion sites to mediate focal adhesion formation, cell migration and
cell cycle progression. Over-expression of FAK has been associated
with invasiveness in a variety of human tumours (Owens et al.,
1995). In interphase, FAK mediates cyclin D1 and p21 CDK inhibitor
expression downstream of integrin engagement. Over-expression
of dominant-negative FAK causes G1 arrest in mouse broblasts
(Zhao et al., 1998). During mitosis, FAK is targeted to the centrosome (Rodriguez-Fernandez et al., 1999), suggesting that FAK may
regulate centrosome functions. This is consistent with the observation that deletion of FAK in endothelial cells leads to multiple
centrosome formation, multi-polar and disorganized mitotic spindles and misalignment of chromosomes during metaphase (Park et
al., 2009).
At the end of mitosis, integrins function to reattach the cells
to its substratum, followed by the establishment of a spread-out
shape and cytoplasmic tension. Similar to cell rounding during
mitosis, these processes are likely regulated by post translational modications of the attachment proteins. Activation of the
anaphase promoting complex/cyclosome (APC/C) during late mitosis may degrade proteins that target the HEF1, zyxin and other
attachment proteins to mitotic structures, thereby allowing focal
contacts to reform. However, the exact mechanism of focal contact re-establishment and reformation of stress bers following
cytokinesis is poorly understood. It remains unclear if the formation
of focal contacts precedes cytoskeletal tension or vice versa. Cells
treated with trypsin also show loss of focal contacts and stress bers
accompanied by cell rounding. However, when replated, these cells
re-establish focal contacts and spreading. Mitotic cells, on the other
hand, stay detached until the completion of mitotic events. It is
likely that cells use distinct mechanisms to promote or inhibit
cytoskeletal events at different stages of cell cycle.
1631
1632
Y.-W. Heng, C.-G. Koh / The International Journal of Biochemistry & Cell Biology 42 (2010) 16221633
Y.-W. Heng, C.-G. Koh / The International Journal of Biochemistry & Cell Biology 42 (2010) 16221633
Nagasaki A, Kanada M, Uyeda TQ. Cell adhesion molecules regulate contractile ringindependent cytokinesis in Dictyostelium discoideum. Cell Res 2009;19:23646.
Nheu T, He H, Hirokawa Y, Walker F, Wood J, Maruta H. PAK is essential for RASinduced upregulation of cyclin D1 during the G1 to S transition. Cell Cycle
2004;3:714.
Niiya F, Tatsumoto T, Lee KS, Miki T. Phosphorylation of the cytokinesis regulator ECT2 at G2 /M phase stimulates association of the mitotic kinase Plk1 and
accumulation of GTP-bound RhoA. Oncogene 2006;25:82737.
Nishimura Y, Yonemura S. Centralspindlin regulates ECT2 and RhoA accumulation
at the equatorial cortex during cytokinesis. J Cell Sci 2006;119:10414.
Oceguera-Yanez F, Kimura K, Yasuda S, Higashida C, Kitamura T, Hiraoka Y, et al.
Ect2 and MgcRacGAP regulate the activation and function of Cdc42 in mitosis. J
Cell Biol 2005;168:22132.
Oegema K, Savoian MS, Mitchison TJ, Field CM. Functional analysis of a human homologue of the Drosophila actin binding protein anillin suggests a role in cytokinesis.
J Cell Biol 2000;150:53952.
Olson MF, Ashworth A, Hall A. An essential role for Rho, Rac, and Cdc42 GTPases in
cell cycle progression through G1 . Science 1995;269:12702.
Owens LV, Xu L, Craven RJ, Dent GA, Weiner TM, Kornberg L, et al. Overexpression
of the focal adhesion kinase (p125FAK) in invasive human tumors. Cancer Res
1995;55:27525.
Park AY, Shen TL, Chien S, Guan JL. Role of focal adhesion kinase Ser-732 phosphorylation in centrosome function during mitosis. J Biol Chem 2009;284:941825.
Perez-Moreno M, Song W, Pasolli HA, Williams SE, Fuchs E. Loss of p120 catenin and
links to mitotic alterations, inammation, and skin cancer. Proc Natl Acad Sci
USA 2008;105:15399404.
Petronczki M, Glotzer M, Kraut N, Peters JM. Polo-like kinase 1 triggers the initiation
of cytokinesis in human cells by promoting recruitment of the RhoGEF Ect2 to
the central spindle. Dev Cell 2007;12:71325.
Piekny AJ, Glotzer M. Anillin is a scaffold protein that links RhoA, actin, and myosin
during cytokinesis. Curr Biol 2008;18:306.
Pokutta S, Drees F, Takai Y, Nelson WJ, Weis WI. Biochemical and structural definition of the l-afadin- and actin-binding sites of alpha-catenin. J Biol Chem
2002;277:1886874.
Pradhan D, Lombardo CR, Roe S, Rimm DL, Morrow JS. alpha-Catenin binds directly
to spectrin and facilitates spectrin-membrane assembly in vivo. J Biol Chem
2001;276:417581.
Pugacheva EN, Roegiers F, Golemis EA. Interdependence of cell attachment and cell
cycle signaling. Curr Opin Cell Biol 2006;18:50715.
Reinsch S, Karsenti E. Orientation of spindle axis and distribution of plasma
membrane proteins during cell division in polarized MDCKII cells. J Cell Biol
1994;126:150926.
Reshetnikova G, Barkan R, Popov B, Nikolsky N, Chang LS. Disruption of the actin
cytoskeleton leads to inhibition of mitogen-induced cyclin E expression, Cdk2
phosphorylation, and nuclear accumulation of the retinoblastoma proteinrelated p107 protein. Exp Cell Res 2000;259:3553.
Reverte CG, Benware A, Jones CW, LaFlamme SE. Perturbing integrin function inhibits
microtubule growth from centrosomes, spindle assembly, and cytokinesis. J Cell
Biol 2006;174:4917.
Rodriguez-Fernandez JL, Gomez M, Luque A, Hogg N, Sanchez-Madrid F, Cabanas C.
The interaction of activated integrin lymphocyte function-associated antigen 1
with ligand intercellular adhesion molecule 1 induces activation and redistribution of focal adhesion kinase and proline-rich tyrosine kinase 2 in T lymphocytes.
Mol Biol Cell 1999;10:1891907.
Rosenblatt J, Cramer LP, Baum B, McGee KM. Myosin II-dependent cortical movement is required for centrosome separation and positioning during mitotic
spindle assembly. Cell 2004;117:36172.
Santamaria D, Barriere C, Cerqueira A, Hunt S, Tardy C, Newton K, et al.
Cdk1 is sufcient to drive the mammalian cell cycle. Nature 2007;448:
8115.
Schaller MD, Borgman CA, Cobb BS, Vines RR, Reynolds AB, Parsons JT. pp125FAK a
structurally distinctive protein-tyrosine kinase associated with focal adhesions.
Proc Natl Acad Sci USA 1992;89:51926.
Schmidt A, Durgan J, Magalhaes A, Hall A. Rho GTPases regulate PRK2/PKN2 to
control entry into mitosis and exit from cytokinesis. EMBO J 2007;26:162436.
Schroeder TE. Cytokinesis: laments in the cleavage furrow. Exp Cell Res
1968;53:2726.
Serra-Pages C, Kedersha NL, Fazikas L, Medley Q, Debant A, Streuli M. The LAR
transmembrane protein tyrosine phosphatase and a coiled-coil LAR-interacting
protein co-localize at focal adhesions. EMBO J 1995;14:282738.
Shakhani SH, Mostov K, Engel J. Focal adhesion components are essential for mammalian cell cytokinesis. Cell Cycle 2008;7:286876.
Shen Y, Schneider G, Cloutier JF, Veillette A, Schaller MD. Direct association of protein-tyrosine phosphatase PTP-PEST with paxillin. J Biol Chem
1998;273:647481.
1633
Spiliotis ET, Kinoshita M, Nelson WJ. A mitotic septin scaffold required for mammalian chromosome congression and segregation. Science 2005;307:17815.
Spiliotis ET, Nelson WJ. Here come the septins: novel polymers that coordinate
intracellular functions and organization. J Cell Sci 2006;119:410.
Straight AF, Field CM, Mitchison TJ. Anillin binds nonmuscle myosin II and regulates
the contractile ring. Mol Biol Cell 2005;16:193201.
Sumi T, Hashigasako A, Matsumoto K, Nakamura T. Different activity regulation and
subcellular localization of LIMK1 and LIMK2 during cell cycle transition. Exp Cell
Res 2006;312:102130.
Thery M, Bornens M. Cell shape and cell division. Curr Opin Cell Biol 2006;18:64857.
Thery M, Racine V, Pepin A, Piel M, Chen Y, Sibarita JB, et al. The extracellular matrix
guides the orientation of the cell division axis. Nat Cell Biol 2005;7:94753.
Toyoshima F, Nishida E. Integrin-mediated adhesion orients the spindle parallel to the substratum in an EB1- and myosin X-dependent manner. EMBO J
2007;26:148798.
Ubersax JA, Woodbury EL, Quang PN, Paraz M, Blethrow JD, Shah K, et al. Targets of
the cyclin-dependent kinase Cdk1. Nature 2003;425:85964.
Uzbekov R, Kireyev I, Prigent C. Centrosome separation: respective role of microtubules and actin laments. Biol Cell 2002;94:27588.
Vadlamudi RK, Adam L, Wang RA, Mandal M, Nguyen D, Sahin A, et al. Regulatable
expression of p21-activated kinase-1 promotes anchorage-independent growth
and abnormal organization of mitotic spindles in human epithelial breast cancer
cells. J Biol Chem 2000;275:3623844.
Wang W, Chen L, Ding Y, Jin J, Liao K. Centrosome separation driven by
actin-microlaments during mitosis is mediated by centrosome-associated
tyrosine-phosphorylated cortactin. J Cell Sci 2008;121:133443.
Wang YL. Dynamics of the cytoskeleton in live cells. Curr Opin Cell Biol
1991;3:2732.
Watabe-Uchida M, Uchida N, Imamura Y, Nagafuchi A, Fujimoto K, Uemura T, et al.
alpha-Catenin-vinculin interaction functions to organize the apical junctional
complex in epithelial cells. J Cell Biol 1998;142:84757.
Watanabe S, Ando Y, Yasuda S, Hosoya H, Watanabe N, Ishizaki T, et al. mDia2 induces
the actin scaffold for the contractile ring and stabilizes its position during cytokinesis in NIH 3T3 cells. Mol Biol Cell 2008;19:232838.
Weiss EE, Kroemker M, Rudiger AH, Jockusch BM, Rudiger M. Vinculin is part of
the cadherin-catenin junctional complex: complex formation between alphacatenin and vinculin. J Cell Biol 1998;141:75564.
Woolner S, OBrien LL, Wiese C, Bement WM. Myosin-10 and actin laments are
essential for mitotic spindle function. J Cell Biol 2008;182:7788.
Wu X, Kocher B, Wei Q, Hammer III JA. Myosin Va associates with microtubulerich domains in both interphase and dividing cells. Cell Motil Cytoskeleton
1998;40:286303.
Yamada S, Pokutta S, Drees F, Weis WI, Nelson WJ. Deconstructing the cadherincatenin-actin complex. Cell 2005;123:889901.
Yamakita Y, Totsukawa G, Yamashiro S, Fry D, Zhang X, Hanks SK, et al. Dissociation
of FAK/p130(CAS)/c-Src complex during mitosis: role of mitosis-specic serine
phosphorylation of FAK. J Cell Biol 1999;144:31524.
Yamamoto M, Marui N, Sakai T, Morii N, Kozaki S, Ikai K, et al. ADP-ribosylation of
the rhoA gene product by botulinum C3 exoenzyme causes Swiss 3T3 cells to
accumulate in the G1 phase of the cell cycle. Oncogene 1993;8:144955.
Yamashiro S, Yamakita Y, Hosoya H, Matsumura F. Phosphorylation of non-muscle
caldesmon by p34cdc2 kinase during mitosis. Nature 1991;349:16972.
Yasuda H, Kanda K, Koiwa H, Suenaga K, Kidou S, Ejiri S. Localization of actin laments
on mitotic apparatus in tobacco BY-2 cells. Planta 2005;222:11829.
Yasuda S, Oceguera-Yanez F, Kato T, Okamoto M, Yonemura S, Terada Y, et al.
Cdc42 and mDia3 regulate microtubule attachment to kinetochores. Nature
2004;428:76771.
Yasuda S, Taniguchi H, Oceguera-Yanez F, Ando Y, Watanabe S, Monypenny J, et
al. An essential role of Cdc42-like GTPases in mitosis of HeLa cells. FEBS Lett
2006;580:337580.
Yoshida S, Kono K, Lowery DM, Bartolini S, Yaffe MB, Ohya Y, et al. Polo-like kinase
Cdc5 controls the local activation of Rho1 to promote cytokinesis. Science
2006;313:10811.
Yuce O, Piekny A, Glotzer M. An ECT2-centralspindlin complex regulates the localization and function of RhoA. J Cell Biol 2005;170:57182.
Zhao J, Bian ZC, Yee K, Chen BP, Chien S, Guan JL. Identication of transcription factor
KLF8 as a downstream target of focal adhesion kinase in its regulation of cyclin
D1 and cell cycle progression. Mol Cell 2003;11:150315.
Zhao JH, Reiske H, Guan JL. Regulation of the cell cycle by focal adhesion kinase. J
Cell Biol 1998;143:19972008.
Zhao WM, Fang G. MgcRacGAP controls the assembly of the contractile ring and the
initiation of cytokinesis. Proc Natl Acad Sci USA 2005;102:1315863.
Zhao ZS, Lim JP, Ng YW, Lim L, Manser E. The GIT-associated kinase PAK targets to
the centrosome and regulates Aurora-A. Mol Cell 2005;20:23749.