Differential Golgi-Exit Mechanism of Homologous Copper P-type ATPases, ATP7A and ATP7B in Polarized Epithelia

Mishra, Monalisa (2023) Differential Golgi-Exit Mechanism of Homologous Copper P-type ATPases, ATP7A and ATP7B in Polarized Epithelia. Masters thesis, Indian Institute of Science Education and Research Kolkata.

Text (MS dissertation of Monalisa Mishra (18MS164)) Thesis_18MS164.pdf - Submitted Version Restricted to Repository staff only Download (2MB)

Abstract

Copper is an essential micronutrient that is required for the proper functioning of many physiological processes in the body. It serves as a cofactor for several enzymes involved in redox reactions. Its role in energy production, including cytochrome c oxidase, superoxide dismutase, and lysyl oxidase, which are critical for cellular respiration, antioxidant protection, and extracellular matrix formation, respectively, making it a vital element for life. Copper homeostasis is tightly regulated in cells, and disruptions in copper metabolism can have severe consequences for cellular function. Mutations in genes that encode copper transporters ATP7A and ATP7B, result in inherited copper disorders such as Menkes disease and Wilson's disease. ATP7A and ATP7B, which are Trans-Golgi network (TGN) resident proteins, traffic to the cell membrane to excrete excess copper out of the cell. In polarised epithelia, these homologous copper ATPases show interesting phenomena: ATP7A traffics to the basolateral surface whereas ATP7B commutes to the apical plasma membrane, upon copper treatment. Therefore, these ATPases serve as a good model to study ligand-mediated polarized sorting at TGN. As a primary aim, I have elucidated intra-TGN localisation of ATP7A and ATP7B in copper-limiting conditions and studies Adaptor proteins (AP) as sorting regulators at TGN. Additionally, I have measured the copper sensitivity of these ATPases. The study was conducted using a combination of immunofluorescence and confocal microscopy.

Actions (login required)

View Item