Regulators of cell division identified
Cell division is a fundamental process of life. Cell biologists have now identified and characterized the signals that control the physical separation of the mother cell into two daughter cells.
Cell division is a tightly controlled process in which a single cell gives rise to two daughter cells. During cell division the duplicated chromosomes are segregated to the two daughter cells by the mitotic spindle apparatus, which consists of protein fibers called microtubules that emanate from the spindle poles. During chromosome segregation the plasma membrane folds in between the segregating chromosomes and physically divides the mother cells into two daughter cells in a process called cytokinesis. Cytokinesis is accomplished by the contraction of a protein ring that assembles underneath the plasmamembrane in the equatorial region of the cell. Formation of the contractile ring is also coordinated by the spindle apparatus, which activates the signaling protein RhoA in small region at the cell equator during chromosome are segregation.
“How cell manages to restrict the activation of RhoA to a small region at the cell equator is an unanswered question in cell biology,” says Esther Zanin, a member of the international collaboration between research groups led by Barbara Conradt (Biozentrum, LMU Munich) and Karen Oegema (University of California at San Diego, USA) that set out to solve the riddle. The spatial restriction of RhoA activation is thought to result from the action of two inhibiting signals, which prevent RhoA activation outside the equatorial region. One of the signals is thought to be transmitted by so-called astral microtubules, which extend in a radial, starburst-like fashion from the spindle poles towards the cell membrane. The second inhibiting signal is believed to be provided by one of the many RhoGAPs , which switch RhoA off, however the identity of the RhoGAP that functions during cell division is unknown. “Therefore it was unclear how the two inhibitory signals function and how they are coordinated,” says Zanin.
The researchers were able to show in the model organism Caenorhabditis elegans that only two of the 23 RhoGAPs are required to modulate RhoA activity during cell division, and both are important for cytokinesis. Screening of the 67 RhoGAPs encoded by the human genome revealed that only one, the so-called MP-GAP, is needed to avoid hyperactivation of RhoA and is essential for the completion of cell cleavage. Notably, however, as long as the astral microtubules are intact, RhoA activity remains restricted to the equatorial region even in the absence of MP-GAP. Only when the astral microtubules are experimentally eliminated does inhibition of MP-GAP lead to the spreading of RhoA activity over the entire periphery of the cell. The next task on the researchers’ agenda is to define the signals emitted by the astral microtubules.
(Developmental Cell 2013) göd