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Tonic NMDA receptor signalling shapes endosomal organisation in mammalian cells

Oleg O Glebov1,2

  • 1Institute of Neuroregeneration and Neurorehabilitation, Qingdao University, Qingdao, 266071, Shandong, China. oleg.glebov@kcl.ac.uk.

Scientific Reports
|June 11, 2020
PubMed

Insights

Calcium signalling via NMDA-type glutamate receptors (NMDARs) controls endosome size in human cells. NMDAR blockade alters endosomal structure, suggesting a role in cancer and membrane trafficking.

Area of Science:

  • Cell Biology
  • Neuroscience
  • Cancer Research

Background:

  • Calcium signalling via NMDA-type glutamate receptors (NMDARs) is crucial for synaptic plasticity in the central nervous system (CNS).
  • NMDARs are expressed beyond the CNS, and aberrant glutamate signalling is implicated in cancer, but their non-CNS function is unclear.

Purpose of the Study:

  • To investigate the role of NMDAR-mediated calcium signalling in cellular processes outside the CNS.
  • To explore the impact of NMDAR function on the endosomal system in various cell types, including cancer cells.

Main Methods:

  • Primary human fibroblasts were treated with calcium-depleted media or NMDAR blockers.
  • Experiments were conducted on primary hippocampal neurons and Jurkat T cells.
  • MDA-MB-231 breast cancer cells were analyzed following NMDAR blockade.

Main Results:

  • Removal of extracellular calcium rapidly decreased early endosome size in human fibroblasts.
  • NMDAR blockade mimicked this effect, while voltage-gated calcium channel (VGCC) blockade did not.
  • NMDAR blockade increased endosome size and decreased their number in MDA-MB-231 breast cancer cells.

Conclusions:

  • Calcium signalling through glutamate receptors regulates the structure of the endosomal system.
  • Aberrations in NMDAR-regulated membrane trafficking may be associated with cancer development.

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