Ankrd45 Is a Novel Ankyrin Repeat Protein Required for Cell Proliferation

Area of Science:

• Molecular Biology
• Cell Biology
• Developmental Biology

Background:

• Ankyrin repeats are common protein-protein interaction motifs found in diverse proteins.
• Ankyrin repeat-containing proteins are involved in various biological functions.
• The specific role of many ankyrin repeat proteins remains largely uncharacterized.

Purpose of the Study:

• To identify and characterize a novel ankyrin repeat-containing protein, Ankrd45.
• To investigate the function of Ankrd45 during zebrafish development and cell proliferation.
• To explore the role of Ankrd45 in cellular processes like mitosis and cytokinesis.

Main Methods:

• Gene identification and cloning of zebrafish ankrd45.
• Zebrafish mutant generation and analysis of developmental phenotypes.
• siRNA and CRISPR/Cas9 mediated knockdown in cultured cells.
• Histological analysis and cell apoptosis assays.
• Confocal microscopy to study protein localization during mitosis.

Main Results:

• Zebrafish ankrd45 exhibits tissue-specific expression in ciliated tissues during development.
• Zebrafish ankrd45 mutants are viable with normal cilia but develop enlarged livers with cysts and apoptosis upon KrasG12V induction.
• ANKRD45 knockdown in cultured cells also induces apoptosis.
• ANKRD45 protein localizes to the midbody ring during cytokinesis.

Conclusions:

• Ankrd45 is a novel ankyrin repeat protein with a conserved role in cell proliferation.
• Ankrd45 plays a role in preventing liver enlargement and apoptosis, particularly under oncogenic stress.
• The protein's localization during mitosis suggests involvement in cell division regulation.