Centralspindlin is a motor complex implicated in cell division. It contributes to virtually every step in
cytokinesis
Cytokinesis () is the part of the cell division process during which the cytoplasm of a single eukaryotic cell divides into two daughter cells. Cytoplasmic division begins during or after the late stages of nuclear division in mitosis and me ...
,
[Glotzer, Michael]
"Cytokinesis: Centralspindlin Moonlights as a Membrane Anchor"
''Current Biology
''Current Biology'' is a biweekly peer-reviewed scientific journal that covers all areas of biology, especially molecular biology, cell biology, genetics, neurobiology, ecology, and evolutionary biology. The journal includes research articles, va ...
'', 18 February 2013 It is highly conserved in animal cells as a component of the spindle midzone and
midbody.
[Glotzer, Michae]
" The 3Ms of central spindle assembly: microtubules, motors and MAPs"
''Nature
Nature, in the broadest sense, is the physical world or universe. "Nature" can refer to the phenomena of the physical world, and also to life in general. The study of nature is a large, if not the only, part of science. Although humans ar ...
'', January 2009 Centralspindlin is required for the assembly of the mitotic spindle
[Nature Publishing Group]
"Research Highlights"
''Cell Migration Consortium'', 2009. Retrieved on 01 March 2014. as well as for microtubule bundling and anchoring of midbody microtubules to the plasma membrane.
This complex is also implicated in tethering the spindle apparatus to the plasma membrane during cytokinesis
[Lekomtsev et al]
''Nature
Nature, in the broadest sense, is the physical world or universe. "Nature" can refer to the phenomena of the physical world, and also to life in general. The study of nature is a large, if not the only, part of science. Although humans ar ...
'', 13 December 2012 This interaction permits cleavage furrow ingression. In addition, centralspindlin's interaction with the
ESCRT III allows for abscission to occur.
Structure
Centralspindlin is a heteroteramer consisting of two different subunit proteins:
# A
KIF23 dimer (Kinesin 6 motor protein, also known as MKLP1 in mammals and ZEN-4 in ''C. elegans'')
::Consists of a motor domain linked to a parallel coiled coil and a globular region by a linker
# A
RACGAP1 dimer (Also known as MgcRacGAP in mammals or CYK-4 in ''C. elegans'')
::Contains a coiled-coil and an important RhoGAP domain
Both KIF23 and RacGAP1 dimerize via their parallel coiled coil domain.
[Pavicic-Kaltenbrunner et al]
"Cooperative assembly of CYK-4/MgcRacGAP and ZEN-4/MKLP1 to form the centralspindlin complex"
''Molecular Biology of the Cell'', 17 October 2007
Centralspindlin oligomerizes in order to link the mitotic spindle with the plasma membrane
The sequences mediating interactions between KIF23 and RacGAP1 are highly variable between species. However, a high affinity interaction between these subunits is essential for the proper functioning of the Centralspindlin complex.
Subunits
KIF23 interacts with microtubules at sites of overlap,
linking the centraspindlin complex to the mitotic spindle.
RacGAP1 recruits
ECT2
Protein ECT2 is a protein that in humans is encoded by the ''ECT2'' gene.
Function
The protein encoded by this gene is a transforming protein that is related to Rho-specific exchange factors and yeast cell cycle regulators. The expression of t ...
to the central spindle.
ECT2 is a Guanine nucleotide-exchange factor for
RhoA
Transforming protein RhoA, also known as Ras homolog family member A (RhoA), is a small GTPase protein in the Rho family of GTPases that in humans is encoded by the ''RHOA'' gene. While the effects of RhoA activity are not all well known, it i ...
. Cytokinesis is initiated when RhoA is activated by ECT2.
[Tatsumoto et a]
"Human Ect2 Is an Exchange Factor for Rho Gtpases, Phosphorylated in G2/M Phases, and Involved in Cytokinesis"
'' Journal of Cell Biology'', 29 November 1999
RacGAP1 is also involved in tethering the central spindle to the plasma membrane. Without this interaction, cytokinesis cannot occur.
Interactions
*A glance at the busy complex
*Interacts with RhoA and Rac during furrow ingression
[Yuce et al]
"An ECT2–centralspindlin complex regulates the localization and function of RhoA"
'' Journal of Cell Biology'', 15 August 2005
*Recruits cytokinetic effector proteins such as ECT2
[Gene Editing Rat Resource Cente]
"Gene-Term Annotation Report"
Retrieved on 01 March 2014
*Binds microtubule plus-end overlaps characteristic of the central spindle through its KIF23 subunit
*Recruits the ESCRT III complex in late cytokinesis
*Promotes cortical accumulation of F-actin and myosin through its RACGAP1 subunit
*Stabilized through interactions with
Aurora B kinase
[Douglas et al]
"Aurora B and 14-3-3 Coordinately Regulate Clustering of Centralspindlin during Cytokinesis"
''Current Biology
''Current Biology'' is a biweekly peer-reviewed scientific journal that covers all areas of biology, especially molecular biology, cell biology, genetics, neurobiology, ecology, and evolutionary biology. The journal includes research articles, va ...
'', 25 May 2010
*Negatively regulated by
14-3-3
*RacGAP1 binds to
PRC1 microtubule crosslinker, an interaction that is crucial for maintaining the stability of the spindle midzone.
References
{{Reflist
Cell biology