Modulators of the synthesis and activity of Annexin A2
We examine the nature of molecular interactions between members of the annexin family and specific mRNA species, with regard to gaining an understanding of their function in vivo.
Annexin A2 is a multifunctional protein and is found in almost all areas of the cell. The protein is equipped with different molecular tags to target it to specific locations and thus different functions within and outside the cell. Annexin A2 has the required properties to function as a key coordinator of neuronal activity-dependent RNP modelling. It is a main protein component of the lumen of exosomes, regulating actin dynamics and transport of vesicles and specific mRNAs, and has the ability to bind lipid rafts and Ca2+, which are all processes important for synaptic plasticity.
Furthermore, it regulates translation of specific mRNAs by binding to their internal ribosomal entry site and may sequester mRNAs in an inactive form (i.e. during transport).
This project will not only be of relevance for basic research in revealing some of the fundamental functions of exosomes, which in turn has implications for the development of exosome-based drugs, but also for the understanding the roles of exosomes in brain tumours and neurological disorders, such as Alzheimer's and Parkinson's Diseases. Thus, this project is potentially of great social and economic benefit through revealing fundamental mechanisms that are aberrantly altered in disease.