The role of anillin/Mid1p during medial division and cytokinesis: from fission yeast to cancer cells

Abstract

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.

Anillin Related Mid1 as an Adaptive and Multimodal Contractile Ring Anchoring Protein: A Simulation Study

“…The Mid1 PH domain's preference for negatively charged PI lipids may indicate a potential role in regulation by phosphorylation, which adds a negatively charged phosphate group to an amino acid. Mid1 is known to be heavily phosphorylated on its N-terminal IDR [7,34], and regulation by phosphorylation is a common feature of other node proteins [49,50]. Similar to Cdc15 [38], progressive phosphorylation of the Mid1 IDR may affect the IDR's association to Mid1's globular domains.…”

“…In model organism Schizosaccharomyces pombe (fission yeast), ring positioning is driven by anillin related protein Mid1 [7], whose spatial localization in the cell middle is regulated by positive cues, such as nuclear shuttling [8] and affinity for PIP 2 that is enriched in the cell middle during mitosis [9], and negative cues, such as phosphoregulation by the kinase Pom1 that localizes at the cell poles away from the cell middle [10]. At the cell center Mid1 organizes cytokinetic "nodes," primarily consisting of myosin Myo2, formin Cdc12, F-BAR domain containing Cdc15, and IQGAP Rng2 [11].…”

The Roles of Septins in Regulating Fission Yeast Cytokinesis

“…The C-terminus of anillin contains three domains: a Rho-binding domain (RBD), a cryptic domain (C2), and a pleckstrin homology domain (PH), and with these functional domains at the C-terminus, anillin associates with PI(4,5)P 2 and interacts with RhoA and septins. In mammalian cells, anillin recruits septins to the cleavage furrow to stabilize the CAR and to promote furrow ingression during cytokinesis [60,62,81].…”

Processes Controlling the Contractile Ring during Cytokinesis in Fission Yeast, Including the Role of ESCRT Proteins

“…However, it only binds the plasma membrane after it is activated and released from the nucleus [20,25]. The roles of Mid1p in positioning the ACR are now well understood in S. pombe and are reviewed in Rezig et al [26], with the mechanism of the medial positioning of the ACR schematically described in Figure 1.…”