Downregulation of TRPV6 channel activity by cholesterol depletion in Jurkat T cell line

Cell Biol Int. 2019 Aug;43(8):965-975. doi: 10.1002/cbin.11185. Epub 2019 Jun 18.

Abstract

Transient receptor potential vanilloid 6 (TRPV6) channels are key players in calcium metabolism of healthy and cancerous cells. Nevertheless, the mechanisms controlling abundance of these channels in plasma membrane of the cells to regulate Ca2+ transport is still poorly understood. In this study, we provide the first evidence that TRPV6 calcium channels and Ca 2+ influx in Jurkat T cell line are modulated by cholesterol, a main lipid component of the plasma membrane. Using patch-clamp technique, we found that activity of TRPV6 channels decreased by cholesterol sequestration with methyl-β-cyclodextrin (MβCD). Continuous measurement of intracellular Ca2+ revealed a reduction of Ca2+ influx into Jurkat cells following cholesterol depletion. Immunofluorescence and immunoelectron microscopy analyses of MβCD-treated cells detected the lower surface expression of the TRPV6 proteins in comparison with control cells. In general, our data showed that cholesterol regulates TRPV6 channel activity and TRPV6-mediated Ca2+ influx in cells, apparently affecting the localization and density of the calcium channels in the plasma membrane of Jurkat T cells.

Keywords: Jurkat T cells; TRPV6 channels; calcium influx; cholesterol; patch-clamp method.

MeSH terms

  • Biological Transport
  • Calcium / metabolism*
  • Calcium Channels / metabolism*
  • Cell Membrane / metabolism*
  • Cholesterol / deficiency*
  • Humans
  • Jurkat Cells
  • Patch-Clamp Techniques / methods
  • TRPV Cation Channels / metabolism*
  • beta-Cyclodextrins / chemistry

Substances

  • Calcium Channels
  • TRPV Cation Channels
  • TRPV6 protein, human
  • beta-Cyclodextrins
  • methyl-beta-cyclodextrin
  • Cholesterol
  • Calcium