Mais complexidade na divisão celular: e você esperava o quê???

terça-feira, novembro 09, 2010

Basic Understanding of Cell Division Reshaped

ScienceDaily (Nov. 8, 2010) — By tracking the flow of information in a cell preparing to split, Johns Hopkins scientists have identified a protein mechanism that coordinates and regulates the dynamics of shape change necessary for division of a single cell into two daughter cells.

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The protein, called 14-3-3, sits at an intersection where it integrates converging signals from within the cell and cues cell shape change and, ultimately, the splitting that allows for normal and abnormal cell growth, such as in tumors.

In a report published Nov. 9 inCurrent Biology, the Hopkins team links 14-3-3 directly to myosin II, a complex of motor proteins that monitors and smoothes out the shape changes to ensure accurate division.

"The discovery of this role for 14-3-3 has immediate and important medical implications because cell division already is one of the major targets of anticancer drugs," says Douglas Robinson, Ph.D., an associate professor of cell biology at the Johns Hopkins School of Medicine. "This protein provides a new opportunity for tweaking the cell division system."The new findings grew out of studies of the so-called mitotic spindle in the one-celled amoeba Dictyostelium. The spindle's job is to separate all the genetic material into two identical sets, one for each daughter cell, and coordinate cell division activities at the cell's outer membrane.
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Read more here/Leia mais aqui: Science Daily

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Current Biology
Volume 20, Issue 21, 9 November 2010, Pages 1881-1889
doi:10.1016/j.cub.2010.09.048

14-3-3 Coordinates Microtubules, Rac, and Myosin II to Control Cell Mechanics and Cytokinesis

Qiongqiong Zhou1, Yee-Seir Kee1, Christopher C. Poirier3, Christine Jelinek2, Jonathan Osborne1, Srikanth Divi1, Alexandra Surcel1, Marie E. Will1, Ulrike S. Eggert5, Annette Müller-Taubenberger6, Pablo A. Iglesias3, Robert J. Cotter2 and Douglas N. Robinson1, 2, 4, , 

1 Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA

2 Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA

3 Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD 21218, USA

4 Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA

5 Dana Farber Cancer Institute and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA

6 Institute for Anatomy and Cell Biology, Ludwig-Maximilians-Universität München, 80336 Munich, Germany

Received 5 April 2010; 
revised 12 August 2010; 
accepted 15 September 2010. 
Published online: October 14, 2010. 
Available online 14 October 2010. 

Summary
Background

During cytokinesis, regulatory signals are presumed to emanate from the mitotic spindle. However, what these signals are and how they lead to the spatiotemporal changes in the cortex structure, mechanics, and regional contractility are not well understood in any system.

Results

To investigate pathways that link the microtubule network to the cortical changes that promote cytokinesis, we used chemical genetics in Dictyostelium to identify genetic suppressors of nocodazole, a microtubule depolymerizer. We identified 14-3-3 and found that it is enriched in the cortex, helps maintain steady-state microtubule length, contributes to normal cortical tension, modulates actin wave formation, and controls the symmetry and kinetics of cleavage furrow contractility during cytokinesis. Furthermore, 14-3-3 acts downstream of a Rac small GTPase (RacE), associates with myosin II heavy chain, and is needed to promote myosin II bipolar thick filament remodeling.

Conclusions

14-3-3 connects microtubules, Rac, and myosin II to control several aspects of cortical dynamics, mechanics, and cytokinesis cell shape change. Furthermore, 14-3-3 interacts directly with myosin II heavy chain to promote bipolar thick filament remodeling and distribution. Overall, 14-3-3 appears to integrate several critical cytoskeletal elements that drive two important processes—cytokinesis cell shape change and cell mechanics.


Graphical Abstract


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