bioRxiv · 10.1101/2024.11.14.623570
PCMD-1 stabilizes the PCM scaffold and facilitates centriole separation
Abstract
Centrosomes are highly dynamic organelles, and maintaining their stability is crucial for spindle pole integrity and bipolar spindle formation. Centrosomes consist of a pair of centrioles surrounded by the pericentriolar material (PCM). In Caenorhabditis elegans, interactions between the PCM scaffold protein SPD-5 and the regulatory kinase PLK-1 are essential for PCM formation and disassembly. However, how PCM stability is established and maintained remains an open question. Here, we address this question by analyzing the function of PCMD-1, a protein that predominantly localizes to centrioles. Mutations in the predicted PLK-1 binding sites of PCMD-1 result in a reduction of centrosomal PLK-1 and PCMD-1 levels, leading to severe distortion of the PCM scaffold. The disorganization of the PCM is already evident during its formation and results in the assembly of a structurally unstable mitotic centrosome, which is unable to resist the microtubule pulling forces exerted on the spindle pole. As a consequence of a weakened PCM scaffold, the pulling forces are not effectively relayed to the entrapped centriole pair, resulting in delayed centriole separation in late anaphase. Together, these findings show that PCMD-1, which predominantly localizes to centrioles and tethers the PCM scaffold to them, is essential for stabilizing the entire PCM scaffold and ensuring timely centriole separation during PCM disassembly. We propose a model in which PCMD-1 initiates the ordered assembly of the PCM scaffold by biasing the PCM core to a certain intrinsic order around the centrioles. This intrinsic order acts as a seed that propagates throughout the surrounding micron-scale PCM scaffold, providing the necessary strength and structural integrity for the centrosome.
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Schreiner, A., Heim, A., Wolff, F., Zanin, E., Mikeladze-Dvali, T.. 2024-11-15. PCMD-1 stabilizes the PCM scaffold and facilitates centriole separation. https://doi.org/10.1101/2024.11.14.623570
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