Mitosis and cytokinesis are undoubtedly the most spectacular parts of the cell cycle. Errors in the choreography of these processes can lead to aneuploidy or genetic instability, fostering cell death or disease. Here, I give an overview of the many mitotic kinases that regulate cell division and the fidelity of chromosome transmission.

Mitotic kinases as regulators of cell division and its checkpoints

Polo-like kinases (Plks) are increasingly recognized as key regulators of mitosis, meiosis and cytokinesis. In agreement with a broad range of proposed functions during cell division, Plks are subject to complex temporal and spatial control. Recent findings are uncovering the mechanisms of Plk regulation, notably their targeting to different cellular structures through interactions with phosphorylated docking proteins. Moreover, information is emerging on the substrate specificity of Plks and the role of individual substrates in M-phase progression.

Polo-like kinases and the orchestration of cell division.

Interactions between microtubules and actin are a basic phenomenon that underlies many fundamental processes in which dynamic cellular asymmetries need to be established and maintained. These are processes as diverse as cell motility, neuronal pathfinding, cellular wound healing, cell division and cortical flow. Microtubules and actin exhibit two mechanistic classes of interactions--regulatory and structural. These interactions comprise at least three conserved 'mechanochemical activity modules' that perform similar roles in these diverse cell functions.

https://dir.nhlbi.nih.gov/labs/lctm/publications/documents/rodriguez_ncb5_599.pdf

Conserved microtubule-actin interactions in cell movement and morphogenesis.

After anaphase onset, animal cells build an actomyosin contractile ring that constricts the plasma membrane to generate two daughter cells connected by a cytoplasmic bridge. The bridge is ultimately severed to complete cytokinesis. Myriad techniques have been used to identify proteins that participate in cytokinesis in vertebrates, insects, and nematodes. A conserved core of about 20 proteins are individually involved with cytokinesis in most animal cells. These components are found in the contractile ring, on the central spindle, within the RhoA pathway, and on vesicles that expand the membrane and sever the bridge. Cytokinesis involves additional proteins, but they, or their requirement in cytokinesis, are not conserved among animal cells.

/pdf/the-molecular-requirements-for-cytokinesis-4qnz42a37f.pdf

The Molecular Requirements for Cytokinesis

Analysis of the kinesin superfamily: insights into structure and function.

Mutations in the Drosophila gene pavarotti result in the formation of abnormally large cells in the embryonic nervous system. In mitotic cycle 16, cells of pav mutant embryos undergo normal anaphase but then develop an abnormal telophase spindle and fail to undertake cytokinesis. We show that the septin Peanut, actin, and the actin-associated protein Anillin, do not become correctly localized in pav mutants. pav encodes a kinesin-like protein, PAV‐KLP, related to the mammalian MKLP-1. In cellularized embryos, the protein is localized to centrosomes early in mitosis, and to the midbody region of the spindle in late anaphase and telophase. We show that Polo kinase associates with PAV‐KLP with which it shows an overlapping pattern of subcellular localization during the mitotic cycle and this distribution is disrupted in pav mutants. We suggest that PAV‐KLP is required both to establish the structure of the telophase spindle to provide a framework for the assembly of the contractile ring, and to mobilize mitotic regulator proteins.

/pdf/pavarotti-encodes-a-kinesin-like-protein-required-to-1r1omj3n0u.pdf

Richard R. Adams

Papers

pavarotti encodes a kinesin-like protein required to organize the central spindle and contractile ring for cytokinesis