Investigating the dynamics of YAP/TAZ mechanosensitive regulators of gene transcription in 2D and 3D using fluorescence microscopy and machine learning

Poster presented as part of the Crick BioImage Analysis Symposium 2023.

AP/TAZ are transcriptional coactivator proteins, they play a key role in many important cellular processes including cell growth, proliferation, wound healing and tumour formation. They move between the nucleus and cytoplasm and alter gene expression through interactions with DNA binding proteins such as TEAD and STAT3. There are multiple mechanisms through which YAP/TAZ is regulated including the Hippo pathway, Wnt signalling, Rho GTPases and mechanical signalling within the cell.

We have chosen to look at Focal Adhesion Kinase (FAK) and its relationship with YAP/TAZ. Previous studies have shown a relationship between the expression of FAK and YAP/TAZ. FAK is very important for the signalling of growth factors and integrins and can primarily be found within adherens junctions and focal adhesions along the plasma membrane. It has kinase and scaffold functions and is able to enter the nucleus when cells are under stress. These are all functionalities which would make it a possible transcriptional regulator for YAP/TAZ.

We have theorised that the levels of YAP/TAZ expression change at different stages of the cell cycle. Previous data has suggested that there is an increase in the levels of YAP expression between S phase and G2. This is an important factor to take into consideration throughout this study as we monitor the change in YAP/TAZ expression under different conditions.

Mechanical signalling plays a large role in the regulation of YAP/TAZ, as they are mechanical sensors which can react to changes within the extracellular environment including changes to cell shape, polarity and binding to the extracellular matrix. This reaction takes place through alteration of transcription through nuclear localisation. As this is a role which YAP/TAZ play throughout the cell, it is an important factor to consider in their own transcriptional regulation.

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