Functional Characterization of Kaptin-Mediated Regulation of Actin Dynamics

Maiti, Ipshita (2025) Functional Characterization of Kaptin-Mediated Regulation of Actin Dynamics. PhD thesis, Indian Institute of Science Education and Research Kolkata.

Text (PhD thesis of Ipshita Maiti (17RS073)) 17RS073.pdf - Submitted Version Restricted to Repository staff only Download (7MB)

Abstract

Kaptin (KPTN) was initially isolated from human platelets in 1992 and identified as a novel actin-binding protein. However, it has remained functionally uncharacterized for decades. Although linked to conditions such as macrocephaly, neurodevelopmental delay, and seizures, its cellular and molecular functions have remained undefined. A dynamic and precisely regulated actin cytoskeleton is essential for normal cellular function. The swift rearrangement of the actin cytoskeleton—essential for processes such as cell survival, proliferation, migration, invasion, phagocytosis, and axonal growth—is mediated by a wide array of actin-binding proteins (ABPs). Among them, capping proteins are key regulators, controlling filament length and stability by preventing monomer addition at filament ends. While numerous actin regulators—such as nucleators, capping proteins, and bundlers—have been well characterized, additional modulators likely exist whose roles remain poorly understood. In this study, we provide the first functional characterization of Kaptin, identifying that KPTN inhibits actin nucleation and acts as a novel barbed-end capping protein, thereby stabilizing actin filaments. Structural modeling using AlphaFold predicts KPTN to be a member of the WD-repeat-containing protein family. We further identify a key cationic residue in the predicted N-terminal β-propeller domain that modulates actin dynamics. Notably, Kaptin inhibits cofilin-mediated actin filament depolymerization, unveiling a previously unrecognized mechanism for stabilizing the actin cytoskeleton. Kaptin-cofilin interaction can lead to a new direction towards the regulation of cofilin in the cell. This dual functionality positions Kaptin as a crucial modulator of actin dynamics, with potential significance in neuronal development and function. By clarifying its molecular role, our study lays the groundwork for future research into Kaptin’s involvement in both cellular architecture and neurodevelopmental processes.

Actions (login required)

View Item