Abstract
The two centrosomes present at the onset of mitosis must separate in a timely and accurate fashion to ensure proper bipolar spindle assembly. The minus-end-directed motor dynein plays a pivotal role in centrosome separation, but the underlying mechanisms remain elusive, particularly regarding how dynein coordinates this process in space and time. We addressed these questions in the one-cell C. elegans embryo, using a combination of 3D time-lapse microscopy and computational modeling. Our analysis reveals that centrosome separation is powered by the joint action of dynein at the nuclear envelope and at the cell cortex. Strikingly, we demonstrate that dynein at the cell cortex acts as a force-transmitting device that harnesses polarized actomyosin cortical flows initiated by the centrosomes earlier in the cell cycle. This mechanism elegantly couples cell polarization with centrosome separation, thus ensuring faithful cell division.
Highlights
Centrosomes are the major microtubule-organizing centers of most animal cells and are critical for directing assembly of the mitotic spindle and, for faithful chromosome segregation
The minus-end-directed motor dynein plays a pivotal role in centrosome separation, but the underlying mechanisms remain elusive, regarding how dynein coordinates this process in space and time
We addressed these questions in the one-cell C. elegans embryo, using a combination of 3D timelapse microscopy and computational modeling
Summary
Centrosomes are the major microtubule-organizing centers of most animal cells and are critical for directing assembly of the mitotic spindle and, for faithful chromosome segregation. Microtubule-associated motor proteins of the kinesin-5 family are required for centrosome separation in several systems (reviewed in Ferenz et al, 2010). These tetrameric plus-end-directed motors can push centrosomes apart by cross-linking and sliding overlapping antiparallel microtubules located between them. Kinesin-5 is partially dispensable for centrosome separation in some systems and completely dispensable in others, including C. elegans (Raaijmakers et al, 2012; Saunders et al, 2007; Tikhonenko et al, 2008). Dynein separates centrosomes in human cells with compromised kinesin-5 function (Raaijmakers et al, 2012). The mechanisms by which dynein governs centrosome separation are only partially understood
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have