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The human GCOM1 complex gene interacts with the NMDA receptor and internexin-alpha.

Raymond S Roginski1, Chi W Lau2, Phillip P Santoiemma3

  • 1Department of Anesthesiology, CMC VA Medical Center, Philadelphia, PA 19104, United States; Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.

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|January 18, 2018
PubMed
Summary

Researchers explored the central nervous system (CNS) roles of the GCOM1 gene, discovering novel GCOM1 interacting proteins (Gints) and a potential neuroprotective pathway involving NMDA receptors.

Keywords:
GRIN1 geneGcom15 proteinGdown1/POLR2MGup1/MYZAPINA geneYeast two-hybrid

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • The GCOM1 gene is known for roles in transcription and cardiac myocytes.
  • Its functions within the central nervous system (CNS) remain largely uncharacterized.

Purpose of the Study:

  • To investigate the CNS functions of the GCOM1 gene.
  • To identify novel GCOM1 interacting proteins and pathways.

Main Methods:

  • Cloning of human and rat brain cDNAs for GCOM1 combined (Gcom) proteins (Gcom15).
  • Yeast two-hybrid (Y2H) screens to identify GCOM1 interacting genes (Gints).
  • Co-expression in heterologous cells and co-immunoprecipitation (co-IP) assays.

Main Results:

  • Identified novel 105-kDa Gcom15 proteins in human and rat brains.
  • Discovered 27 novel Gints, including synaptic proteins implicated in neurologic diseases.
  • Demonstrated Gcom15 interaction with the NR1 subunit of the NMDA receptor (NMDAR).
  • Showed co-IP of GCOM1 proteins with internexin-alpha (INA), an NMDAR interactor.

Conclusions:

  • GCOM1 plays a role in the CNS, interacting with the NMDAR.
  • A novel GCOM1-GRIN1-INA interaction pathway suggests potential neuroprotective mechanisms.