Overexpression of the dopamine receptor‐interacting protein Alix/AIP1 modulates NMDA receptor‐triggered cell death

Alix/AIP1 is an adaptor protein involved in apoptosis, endocytic membrane trafficking and brain development. Alix has been found within the human postsynaptic density (PSD) and, since NMDA receptors (NMDARs) are central components of the PSD, we hypothesized that the close proximity of both proteins may allow Alix to influence the downstream pathways following NMDAR activation. NMDARs play important roles in excitotoxicity, and we evaluated the effects of recombinant Alix in an NMDAR cell death assay. Overexpression of Alix with NMDARs increases the potency of NMDAR‐ induced cell death compared to cells expressing only NMDARs, and this requires expression of the Alix C‐terminal region. Therefore, we demonstrate a previously unreported role for Alix as a potential modulator of NMDAR function.