Dataset Information

Functional analysis of a human homologue of the Drosophila actin binding protein anillin suggests a role in cytokinesis.

ABSTRACT: We have characterized a human homologue of anillin, a Drosophila actin binding protein. Like Drosophila anillin, the human protein localizes to the nucleus during interphase, the cortex following nuclear envelope breakdown, and the cleavage furrow during cytokinesis. Anillin also localizes to ectopic cleavage furrows generated between two spindles in fused PtK(1) cells. Microinjection of antianillin antibodies slows cleavage, leading to furrow regression and the generation of multinucleate cells. GFP fusions that contain the COOH-terminal 197 amino acids of anillin, which includes a pleckstrin homology (PH) domain, form ectopic cortical foci during interphase. The septin Hcdc10 localizes to these ectopic foci, whereas myosin II and actin do not, suggesting that anillin interacts with the septins at the cortex. Robust cleavage furrow localization requires both this COOH-terminal domain and additional NH(2)-terminal sequences corresponding to an actin binding domain defined by in vitro cosedimentation assays. 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. These results indicate that anillin is a conserved cleavage furrow component important for cytokinesis. Interactions with at least two other furrow proteins, actin and the septins, likely contribute to anillin function.

SUBMITTER: Oegema K

PROVIDER: S-EPMC2175195 | biostudies-literature | 2000 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Functional analysis of a human homologue of the Drosophila actin binding protein anillin suggests a role in cytokinesis.

Oegema K K Savoian M S MS Mitchison T J TJ Field C M CM

The Journal of cell biology 20000801 3

We have characterized a human homologue of anillin, a Drosophila actin binding protein. Like Drosophila anillin, the human protein localizes to the nucleus during interphase, the cortex following nuclear envelope breakdown, and the cleavage furrow during cytokinesis. Anillin also localizes to ectopic cleavage furrows generated between two spindles in fused PtK(1) cells. Microinjection of antianillin antibodies slows cleavage, leading to furrow regression and the generation of multinucleate cells ...[more]

PMID: 10931866

Similar Datasets

Project description:Background & aimsCytokinesis can fail during normal postnatal liver development, leading to polyploid hepatocytes. We investigated whether inhibiting cytokinesis in the liver slows tumor growth without compromising the health of normal hepatocytes. We inhibited cytokinesis in cancer cells by knocking down ANLN, a cytoskeletal scaffolding protein that regulates cytokinesis and might promote tumorigenesis, in mice with liver disease.MethodsWe analyzed clinical and gene expression data from The Cancer Genome Atlas, Oncomine, PrognoScan, and a hepatocellular carcinoma (HCC) tissue microarray. We knocked down ANLN with small interfering RNAs (siRNAs) in H2.35 liver cells and performed image analyses of cells undergoing cytokinesis. siRNAs were delivered to LAP-MYC mice, which develop hepatoblastoma, using lipid nanoparticles. H2.35 cells with knockdown of ANLN or control cells were injected into FRG mice, which develop chronic liver damage, and tumor growth was monitored. We also developed mice with inducible expression of transgenes encoding small hairpin RNAs (shRNAs) against Anln messenger RNA and studied liver tumorigenesis after administration of diethylnitrosamine and carbon tetrachloride. siRNAs against Anln messenger RNA were conjugated to N-acetylgalactosamine to reduce toxicity and increase hepatocyte tropism; their effects were studied in mouse models of liver cancer and regeneration.ResultsLevels of ANLN messenger RNA were increased in human HCC tissues compared to non-tumor liver tissues. siRNA knockdown of ANLN blocked cytokinesis in H2.35 liver cells. Administration of siRNA against ANLN increased survival times of LAP-MYC mice, compared to mice given a control siRNA. H2.35 liver cells with shRNA knockdown of ANLN formed tumors more slowly in FRG mice than control H2.35 cells. Mice with inducible expression of shRNAs against Anln mRNA developed fewer liver tumors after administration of diethylnitrosamine and carbon tetrachloride than control mice. Knockdown of ANLN did not affect liver regeneration after acute and chronic liver injuries.ConclusionsKnockdown of ANLN in liver cells blocks cytokinesis and inhibits development of liver tumors in mice. Agents that inhibit ANLN in the liver might be effective for prevention or treatment of HCC.

Dataset Information

Functional analysis of a human homologue of the Drosophila actin binding protein anillin suggests a role in cytokinesis.

Publications

Functional analysis of a human homologue of the Drosophila actin binding protein anillin suggests a role in cytokinesis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets