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.