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

Sharifah Salim1, Jamal Nasir2, Philip E Chen1

  • 1Centres for Biomedical Sciences and Gene & Cell Therapy, School of Biological Sciences, Royal Holloway, University of London, Egham, Surrey, UK.

FEBS Letters
|May 12, 2019
PubMed

Insights

Alix (AIP1) protein enhances NMDAR-induced cell death, suggesting a role in modulating NMDAR function. This effect requires the Alix C-terminal region, highlighting its importance in neuronal pathways.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Alix/AIP1 is an adaptor protein implicated in apoptosis, endocytic trafficking, and brain development.
  • Alix is localized to the postsynaptic density (PSD), a key structure containing NMDA receptors (NMDARs).

Purpose of the Study:

  • To investigate the potential role of Alix in modulating downstream signaling pathways following NMDAR activation.
  • To determine the effect of Alix on NMDAR-mediated excitotoxicity.

Main Methods:

  • Utilized a cell death assay to evaluate the impact of recombinant Alix on NMDAR-induced cell death.
  • Examined the necessity of the Alix C-terminal region for its effect on NMDAR function.

Main Results:

  • Overexpression of Alix potentiated NMDAR-induced cell death.
  • The observed potentiation of cell death required the expression of the Alix C-terminal region.

Conclusions:

  • Alix acts as a potential modulator of NMDAR function.
  • This study reveals a novel role for Alix in excitotoxicity and NMDAR signaling pathways.
Keywords:
ALG-2PDCD6IPcalciumdopamine receptor interacting proteinglutamate receptorneurodegeneration

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