Life Sciences & Biotechnology
Title : | Dissecting the mechanisms of cleavage furrow formation during anaphase in animal cells |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Cell Biology, Developmental Biology |
Principal Investigator : | Prof. Sachin Kotak, Indian Institute Of Science, Bangalore, Karnataka |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | sachin.kotak@mcbl.iisc.ernet.in |
Details
Executive Summary : | The separation of sister chromatids in anaphase is closely linked to cleavage furrow formation, which is crucial for accurate DNA and cellular partitioning. This process is regulated by membrane-localized dynein, which can walk along astral microtubules, generating pulling forces that aid in mitotic spindle elongation and chromosome separation. The cleavage furrow formation is initiated by local activation of RhoA, which controls actin polymerization and myosin II activation at the equatorial membrane. At the onset of anaphase, coordinated assemblies of multiple protein complexes at the spindle midzone regulate the spatiotemporal activation of RhoA at the equatorial membrane. Centralspindlin, a critical complex formed at the spindle midzone, regulates RhoA activation at the equatorial membrane. However, the underlying molecular mechanisms by which the presence of NuMA/dynein at the polar region of the cell membrane restricts the localization of Ect2/Cyk4/Mklp1-based complexes, and thus RhoA at the equatorial membrane, remain unknown. This study aims to investigate how NuMA/dynein-based complexes ensure confined localization of Ect2/Cyk4/Mklp1. This proposal combines cell and molecular biology approaches, including FRAP analysis and computational biology, to investigate the molecular pathways by which NuMA/dynein/dynactin complexes polarize Ect2/Cyk4/Mklp1. The outcome of this work has implications beyond fundamental science discovery, as proper cleavage furrow formation is critical for development and morphogenesis, and improper cytokinesis can lead to genomic instability, which is often seen in various cancer conditions. |
Total Budget (INR): | 44,03,680 |
Organizations involved