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Ankrd45 Is a Novel Ankyrin Repeat Protein Required for Cell Proliferation.

ABSTRACT: Ankyrin repeats, the most common protein-protein interaction motifs in nature, are widely present in proteins of both eukaryotic and prokaryotic cells. Ankyrin repeat-containing proteins play diverse biological functions. Here, we identified the gene ankrd45, which encodes a novel, two ankyrin repeat-containing protein. Zebrafish ankrd45 displayed a tissue specific expression pattern during early development, with high expression in ciliated tissues, including otic vesicles, Kupffer's vesicles, pronephric ducts, and floor plates. Surprisingly, zebrafish ankrd45 mutants were viable and developed grossly normal cilia. In contrast, mutant larvae developed enlarged livers when induced with liver specific expression of Kras^G12V, one of the common mutations of KRAS that leads to cancer in humans. Further, histological analysis suggested that multiple cysts developed in the mutant liver due to cell apoptosis. Similarly, knockdown of ANKRD45 expression with either siRNA or CRISPR/Cas9 methods induced apoptosis in cultured cells, similar to those in zebrafish ankrd45 mutant livers after induction. Using different cell lines, we show that the distribution of ANKRD45 protein was highly dynamic during mitosis. ANKRD45 is preferably localized to the midbody ring during cytokinesis. Together, our results suggest that Ankrd45 is a novel ankyrin repeat protein with a conserved role during cell proliferation in both zebrafish embryos and mammalian cells.

SUBMITTER: Kang Y

PROVIDER: S-EPMC6628321 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Ankrd45 Is a Novel Ankyrin Repeat Protein Required for Cell Proliferation.

Kang Yunsi Y Xie Haibo H Zhao Chengtian C

Genes 20190616 6

Ankyrin repeats, the most common protein-protein interaction motifs in nature, are widely present in proteins of both eukaryotic and prokaryotic cells. Ankyrin repeat-containing proteins play diverse biological functions. Here, we identified the gene ankrd45, which encodes a novel, two ankyrin repeat-containing protein. Zebrafish ankrd45 displayed a tissue specific expression pattern during early development, with high expression in ciliated tissues, including otic vesicles, Kupffer's vesicles, ...[more]

PMID: 31208154

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Project description:Background:Left ventricular assist devices (LVADs) have revolutionized and improved the care of the sickest heart failure (HF) patients, and it is imperative that they receive appropriate ventricular unloading. Assessing this critical parameter with current methodologies (labs, imaging) is usually suboptimal in this patient population. Hence it is imperative to elucidate the molecular underpinnings involved in ventricular unloading. We have previously identified the cytoskeletal protein ?II spectrin as an essential nodal protein involved in post-translational targeting and ?II spectrin protein levels are significantly altered in multiple forms of human and animal HF. We therefore hypothesized that the ?II spectrin pathway would play a critical role in LVAD remodeling. Methods:Human heart failure samples were obtained from patients undergoing heart transplantation. Wild type (WT) mice and our previously validated ?II spectrin conditional knock out (?II cKO) mice were used for animal experiments. Transaortic constriction (TAC) was performed on WT mice. Protein expression was assessed via immunoblots, and protein interactions were assessed with co-immunoprecipitation. Transcriptome analysis was performed using isolated whole hearts from control adult WT mice (n = 3) compared to ?II cKO spectrin mice (n = 3). Results:We report that hearts from mice selectively lacking ?II spectrin expression in cardiomyocytes displayed altered transcriptional regulation of cardiac ankyrin repeat protein (CARP). Notably, CARP protein expression is increased after TAC. Additionally, our findings illustrate that prior to LVAD support, CARP levels are elevated in HF patients compared to normal healthy controls. Further, for the first time in a LVAD population, we show that elevated CARP levels in HF patients return to normal following LVAD support. Conclusion:Our findings illustrate that CARP is a dynamic molecule that responds to reduced afterload and stress, and has the potential to serve as a prognostic biomarker to assess for an adequate response to LVAD therapy.

Dataset Information

Ankrd45 Is a Novel Ankyrin Repeat Protein Required for Cell Proliferation.

Publications

Ankrd45 Is a Novel Ankyrin Repeat Protein Required for Cell Proliferation.

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