Mechanistic insights into kindlin function and regulation

Abstract

Kindlins are FERM domain containing adapter proteins known for their role in integrin inside-out and outside-in activation and signalling. In addition, they mediate various integrin-independent processes. How kindlins perform diverse functions under different cellular contexts is not yet fully elucidated. Here, regulatory mechanisms behind kindlin and integrin activity with respect to their post-translational modifications and interacting partners are explored. The first part of thesis addresses auto-inhibitory mechanism of kindlin-3 oligomerization. Kindlin-3 trimer formation was validated in vitro, and disruption of trimerization resulted in increased integrin-mediated cell spreading and adhesion. In the second part, newly identified interaction of kindlin-3 is explored, uncovering its role in translational regulation. Overall, findings on intra- and inter-molecular interactions of kindlins have opened up new areas for exploration of their functions and potential implications in disease progression.