Cytokinesis is the final stage of the cell cycle which separates cellular constituents to produce two daughter cells. Using the fission yeast Schizosaccharomyces pombe we have investigated the role of various classes of proteins involved in this process. Central to these is anillin/Mid1p which forms a ring-like structure at the cell equator that predicts the site of cell separation through septation in fission yeast. Here we demonstrate a direct physical interaction between Mid1p and the endosomal sorting complex required for transport (ESCRT)-associated protein Vps4p, a genetic interaction of the mid1 and vps4 genes essential for cell viability, and a requirement of Vps4p for the correct cellular localization of Mid1p. Furthermore, we show that Mid1p is phosphorylated by aurora kinase, a genetic interaction of the mid1 and the aurora kinase ark1 genes is essential for cell viability, and that Ark1p is also required for the correct cellular localization of Mid1p. We mapped the sites of phosphorylation of Mid1p by human aurora A and the polo kinase Plk1 and assessed their importance in fission yeast by mutational analysis. Such analysis revealed serine residues S332, S523 and S531 to be required for Mid1p function and its interaction with Vps4p, Ark1p and Plo1p. Combined these data suggest a physical interaction between Mid1p and Vps4p important for cytokinesis, and identify phosphorylation of Mid1p by aurora and polo kinases as being significant for this process.
Cytokinesis is the final stage of cell division cycle when cellular constituents are separated to produce two daughter cells. This process is driven by the formation and constriction of a contractile ring. Progression of these events is controlled by mechanisms and proteins that are evolutionary conserved in eukaryotes from fungi to humans. Genetic and molecular studies in different model organisms identified essential cytokinesis genes, with several conserved proteins, including the anillin/Mid1p proteins, constituting the core cytokinetic machinery. The fission yeast Schizosaccharomyces pombe represents a well-established model organism to study eukaryotic cell cycle regulation. Cytokinesis in fission yeast and mammalian cells depends on the placement, assembly, maturation, and constriction of a medially located actin-myosin contractile ring (ACR). Here, we review aspects of the ACR assembly and cytokinesis process in fission yeast and consider the regulation of such events in mammalian cells. First, we briefly describe the role of anillin during mammalian ACR assembly and cytokinesis. Second, we describe different aspects of the anillin-like protein Mid1p regulation during the S. pombe cell cycle, including its structure, function, and phospho-regulation. Third, we briefly discuss Mid1pindependent ACR assembly in S. pombe. Fourth, we highlight emerging studies demonstrating the roles of anillin in human tumourigenesis introducing anillin as a potential drug target for cancer treatment. Collectively, we provide an overview of the current understanding of medial division and cytokinesis in S. pombe and suggest the implications of these observations in other eukaryotic organisms, including humans.
26Cytokinesis is the final stage of the cell cycle which separates cellular constituents to 27 produce two daughter cells. Using Schizosaccharomyces pombe we have 28 investigated the role of various classes of proteins involved in this process. Central to 29 these is anillin/Mid1p which forms a ring-like structure at the cell equator that predicts 30 the site of cell separation through septation in fission yeast. Here we demonstrate a 31 direct physical interaction between Mid1p and the endosomal sorting complex 32 required for transport (ESCRT)-associated protein Vps4p. The interaction is essential 33 for cell viability, and Vps4p is required for the correct cellular localization of Mid1p. 34Furthermore, we show that Mid1p is phosphorylated by the aurora kinase Aurora A, 35that the interaction of mid1 and ark1 genes is essential for cell viability, and that 36Ark1p is also required for the correct cellular localization of Mid1p. We mapped the 37 sites of phosphorylation of Mid1p by Aurora A and the polo kinase Plk1 and 38 assessed their importance by mutational analysis. Mutational analysis revealed 39 S332, S523 and S531 to be required for Mid1p function and its interaction with 40Vps4p, Ark1p and Plo1p. Combined our data suggest a physical interaction between 41Mip1p and Vps4p important for cytokinesis, and identify phosphorylation of Mid1p by 42 aurora and polo kinases as being significant for this process. 43 44 Author summary 45Replication is a property of all living cells, with cell separation, so-called cytokinesis, 46 the final step in the process. A large number of proteins have been identified that are 47 complex required for transport (ESCRT) proteins and the anillin protein Mid1p. We 51 identify a direct physical interaction between the ESCRT protein Vps4 and 52 anillin/Mid1p, and explore how it regulates cytokinesis. Midp1 activity is shown to 53 controlled by the protein kinase Ark1p by direct phosphorylation, and this 54 phosphorylation is important for Mid1p function. These observations identify new 55 ways in which ESCRT and anillin/Mid1p control cell separation. 56 57
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