Cellular and tissue specific expression and functional analysis of Kaptin

Banerjee, Aishwarya (2025) Cellular and tissue specific expression and functional analysis of Kaptin. PhD thesis, Indian Institute of Science Education and Research Kolkata.

Text (PhD thesis of Aishwarya Banerjee (20RS003)) 20RD003.pdf - Submitted Version Restricted to Repository staff only Download (3MB)

Abstract

Kaptin was initially identified as an actin-interacting protein, isolated from the soluble fraction of blood platelets using F-actin chromatography. It localizes to actin-rich regions of cells, including the lamellipodia and filopodia of motile fibroblasts, the stereocilia of inner ear hair cells, and the growth cones of developing neurons which are sites characterized by rapid actin cytoskeletal remodelling. Kaptin has also been found to be a component of the KICSTOR protein complex, which suppresses the mTORC1 signalling pathway during amino acid and nutrient deprivation. Dysregulation of mTORC1 signalling, namely hyperactivity of signalling pathway is implicated in various diseases, such as cancer, epilepsy, and certain neurodevelopmental disorders. A kaptin loss-of-function mouse model revealed hyperactivation of the mTORC pathway in the absence of kaptin, mirroring behavioural and cognitive phenotypes which were observed in humans with kaptin mutations. These phenotypes included cranial abnormalities, anxiety, seizures, and increased brain size and volume, supporting the classification of kaptin-related neurodevelopmental disorders as mTORopathies. Further biochemical studies have shown that kaptin functions as a weak barbed-end actin-capping protein, structurally and functionally resembling members of the coronin family, which contains WD-repeat domains. In this study, we investigated the expression pattern of kaptin at both mRNA and protein levels across various murine tissues derived from all three germ layers at different developmental stages (0, 15, 30, and 60 days), as well as in a range of cancerous and non-cancerous cell lines. Our aim was to explore kaptin’s role in modulation of cytoskeletal dynamics across diverse cell and tissue types. Additionally, we examined kaptin’s functional significance in cellular processes involving dynamic cytoskeletal rearrangement, such as cell migration, invasion, and viability. Notably, overexpression of kaptin in HeLa cells led to a reduction in cell viability, migration, and invasion, highlighting its potential role in regulating these processes.

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