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Developmental biology - Cell Division|
Cell division is fundamental to life
Correct chromosome segregation requires precise cleavage in the mid-plane of a cell.
To achieve this, the spindle apparatus sends out two signals. One actively stimulates formation of the contractile ring at the mid-plane of a cell; a second signal inhibits the contractile ring from assembling at either pole of the cell. The inhibitory signal originates from the astral microtubules, which project into the cell poles after formation of the spindle apparatus begins.
"The molecular constituents of this signal had been unknown until now. With the help of a newly developed and highly sensitive microscope method, we now show in the nematode Caenorhabditis elegans (C. elegans) - a popular model organism in cell biology - that the enzyme Aurora A is a central component of that inhibitory signal."
Aurora A, is also present in human cells, and known to play a crucial role in control of spindle assembly, and is also activated on astral microtubules.
"We think that the active enzyme then diffuses from the astral microtubules to the cell membrane at the cell poles, where it suppresses formation of a contractile ring."
The precise control of cell division is not only essential in embryo development, but also in the adult organism. Defects in cell division can causes numerous diseases including cancers.
"A detailed understanding of this fundamental process is therefore a prerequisite for the development of more effective ways to treat and prevent such disorders," explains Zanin.
During cytokinesis, a signal from the central spindle that forms between the separating anaphase chromosomes promotes the accumulation of contractile ring components at the cell equator, while a signal from the centrosomal microtubule asters inhibits accumulation of contractile ring components at the cell poles. However, the molecular identity of the inhibitory signal has remained unknown. To identify molecular components of the aster-based inhibitory signal, we developed a means to monitor the removal of contractile ring proteins from the polar cortex after anaphase onset. Using this assay, we show that polar clearing is an active process that requires activation of Aurora A kinase by TPXL-1. TPXL-1 concentrates on astral microtubules coincident with polar clearing in anaphase, and its ability to recruit Aurora A and activate its kinase activity are essential for clearing. In summary, our data identify Aurora A kinase as an aster-based inhibitory signal that restricts contractile ring components to the cell equator during cytokinesis.
Authors: Sriyash Mangal, Jennifer Sacher, Taekyung Kim, Daniel Sampaio Osório, Fumio Motegi, Ana Xavier Carvalho, Karen Oegema, Esther Zanin.
Reference material: Dynamics of Microtubules.
After six months this article is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
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C. elegans embryo in final stages of cell division (1. MAGENTA: microtubules; 2. BLUE: TPXL-1; 3. GREEN: chromosomes). Image credit: Zanin, lab, LMU.