Modulating the Motion; The Role of Rpt2, an ATPase in Collective Cell Migration

Mohan, Anjali (2025) Modulating the Motion; The Role of Rpt2, an ATPase in Collective Cell Migration. Masters thesis, Indian Institute of Science Education and Research Kolkata.

Text (MS Dissertation of Anjali Mohan (20MS217)) 20MS217_Thesis_file.pdf - Submitted Version Restricted to Repository staff only Download (2MB)

Abstract

Collective migration of cells is prevalent in many instances in metazoans essentially contributing to development and survival. Unfortunately, the mechanism of migration is exploited in many diseases like cancer. So, to understand the basic biology and pathology of disease, studying collective cell migration is important. Collectively migrating cells must polarize, dynamically remodel adhesive structures and extend protrusions in order to successfully migrate. The dynamicity is maintained by regulating the turnover of different proteins that are involved in Actin polymerisation, signalling molecules such as Rho and Rac and guidance molecules within each cell. The ubiquitin- proteasome system is the main machinery responsible for protein quality control in a cell. Moreover, over the past few decades, proteasomal inhibitors are being used to treat metastatic tumour. However, how mechanistically proteasome is regulating the collective movement of cells is poorly understood. So, here I tried to explore this aspect by selectively downregulating one of the key subunits of 26S proteasome, Rpt2, a component of base of 19S particle in the context of border cell migration. Rpt2 depletion shows significant defect in migration. Using real time imaging, it was shown that Rpt2 regulate protrusion dynamics. Additionally, the study gives key insights into the role of Rpt2 in modulating the localisation of Armadillo and levels of Actin in the migrating cluster.

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