Probing the Mint2 Protein-Protein Interaction Network Relevant to the Pathophysiology of Alzheimer's Disease

The intracellular adaptor protein Mint2 binds amyloid precursor protein (APP) and presenilin-1, which are both central constituents of the amyloidogenic pathway associated with Alzheimer's disease (AD). Additional interaction partners have also been suggested for Mint2; several of them are also pertinent to AD pathogenesis. However, no comparative mapping of the Mint2 protein-protein interaction network is available. Here we provide a systematic characterization of seven interaction partners and address their specificities towards the different binding domains of Mint2, which reveal domain-specific and -nonspecific interaction partners. Moreover, we show that the last two C-terminal amino acids of Mint2 are both important for the intramolecular interaction with the PDZ1 domain and for the stability of Mint2.