Amyloid Precursor Protein: An adhesion protein and a novel talin binder

Amyloid precursor protein (APP), the amyloid plaque forming protein, hypothesised to be involved in the development of Alzheimer's disease (AD) is an adhesion protein which localises to focal adhesions. The amyloid cascade hypothesis has resulted in the role of APP in adhesions being largely overlooked and understudied. This research provides the first experimental evidence of a novel protein interaction between APP and talin, another adhesion protein, and highlights a novel role of APP within focal adhesions. This protein interaction, shown here for the first time, highlights a new set of mechanical linkages available to cells within adhesions. Several biochemical and biophysical techniques were employed to investigate and characterise this interaction including Fluorescence Polarisation, Nuclear Magnetic Resonance and Microscale Thermophoresis. These techniques supported a direct interaction between the F2F3 domain of talin and the intracellular domain of APP. We were also able to show that this interaction is stronger in the presence of a lipid bilayer which mimics a cellular membrane. Both talin and APP are involved in several biological functions and so their ability to interact suggests an abundance of new nteractions between the binding partners of each protein when undertaking different roles. Importantly within neuroscience, this interaction may be crucial in shedding light on discrepancies within the amyloid cascade hypothesis and may well provide the basis for a more comprehensive explanation of AD onset.