Disease relevance of scra

• Gene expression profile analysis of non-small cell lung cancers (NSCLC) and subsequent functional analyses revealed that human ANLN, a homologue of anillin, an actin-binding protein in Drosophila, was transactivated in lung cancer cells and seemed to play a significant role in pulmonary carcinogenesis [1].

High impact information on scra

• In contrast, peripheral MTs still probe the cortex and form regions of overlap that recruit the Pav-KLP motor and Aurora B kinase. orbit mutants have disorganized or incomplete anillin and actin rings, and although cleavage furrows initiate, they ultimately regress [2].
• Functional analysis of a human homologue of the Drosophila actin binding protein anillin suggests a role in cytokinesis [3].
• Like Drosophila anillin, the human protein localizes to the nucleus during interphase, the cortex following nuclear envelope breakdown, and the cleavage furrow during cytokinesis [3].
• Endogenous anillin and Hcdc10 colocalize to punctate foci associated with actin cables throughout mitosis and the accumulation of both proteins at the cell equator requires filamentous actin [3].
• In contractile rings, metaphase furrows, and nascent ring canals, anillin remains bound to the invaginated cortex suggesting a stabilizing role [4].

Biological context of scra

• Anillin is not expressed in cells that have left the cell cycle [4].
• By immunofluorescence, anillin localizes to the nucleus of interphase cells, except in the syncytial embryo where it is always cytoplasmic [4].
• We characterize defects in cellularization, pole cell formation and cytokinesis in a series of maternal effect and zygotic anillin alleles [5].
• Our results highlight specialization of divergent anillin family proteins in the C. elegans life cycle and reveal conserved roles for this protein family in organizing syncytial structures and cortical contractility [6].
• However late telophases of both cell types displayed persistent midbodies associated with disorganized F actin and anillin structures [7].

Anatomical context of scra

• We speculate that anillin plays a role in organizing and/or stabilizing the cleavage furrow and other cell cycle regulated, contractile domains of the actin cytoskeleton [4].
• Cumulatively, our data point to an important role for Anillin in scaffolding cleavage furrow components, directly stabilizing intracellular bridges, and indirectly stabilizing newly deposited plasma membrane during cellularization [5].
• Depletion of anillin in Drosophila or human cultured cells results in cytokinesis failure [8].
• Double-mutant analysis between scraps, a mutation in anillin that eliminates microfilament rings, and bottleneck suggests that microfilaments can still contract even though they are not organized into rings [9].
• Examination of fixed preparations of mutant spermatocytes showed contractile rings of anillin and actin that were of normal appearance at early stages but were larger and less well organised at later stages of cytokinesis than in wild-type cells [10].

Physical interactions of scra

• Anillin binds nonmuscle myosin II and regulates the contractile ring [8].

Regulatory relationships of scra

• In addition to its role in activating RhoA signalling, RacGAP50C also controls the proper assembly of the actomyosin ring by interacting with Anillin at the cleavage furrow [11].

Other interactions of scra

• Anillin is a conserved component of the contractile ring that is essential for cytokinesis, and physically interacts with three conserved cleavage furrow proteins, F-actin, myosin II and septins in biochemical assays [5].
• In sharp contrast, in ovarian ring canals, septins have not been detected, anillin is lost from mature ring canals and filamentous actin is a major component [12].
• In chickadee and KLP3A mutant ana-telophases the cortical anillin band fails to constrict, indicating that its contraction is normally driven by the cytokinetic ring [13].
• These findings, coupled with the analysis of anillin behavior in twinstar mutants, suggested a model on the role of anillin during cytokinesis [13].
• In contrast, septin-based structures rearrange and disassemble in cells, which might be controlled by diverse factors (e.g., the Cdc42-borg system, anillin, syntaxin, phospholipids) and covalent modifications (e.g., phosphorylation, ubiquitination, sumoylation) [14].

Analytical, diagnostic and therapeutic context of scra

• Anillin migrates at 190 kD on SDS-PAGE [4].

References