Investigating signalling links between integrin-mediated adhesion complexes and the mechanistic target of rapamycin complex 1 (mTORC1) pathway

Abstract

Adhesion of cells to the surrounding extracellular matrix (ECM) is required for a metazoan existence, enabling cells to migrate and signal appropriately in response to changes in their environment. Plasma membrane integrin receptors are key mediators of cell-ECM adhesion: they bind a range of ECM molecules at focal sites, trigger the recruitment of > 200 intracellular components, and form large adhesion complexes at the cytoplasmic face of the plasma membrane. While it is well established that adhesion signalling cooperates extensively with other canonical signalling pathways to control cell fate decisions, a comprehensive systems-level understanding of how these interactions occur is lacking. Perturbation of key signalling nodes and subsequent proteomic analysis of integrin-mediated adhesion complexes may provide insight into how these signalling communications are organised. In this thesis, a mass spectrometry (MS)-based proteomic approach was used to investigate how perturbation of mechanistic target of rapamycin complex 1 (mTORC1) signalling affects the recruitment of proteins to or from integrin-mediated adhesion complexes. Initial analyses indicate that translation initiation factors are lost from integrin-mediated adhesion complexes upon mTORC1 inhibition, suggesting that mTORC1-regulated protein translation may occur at these sites. Further repeat data assessing phosphorylation changes in addition to total protein changes is required to determine whether these preliminary observations are significant.

Date of Award	1 Aug 2015
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Martin Humphries (Supervisor) & Martin Pool (Supervisor)