Galactosylceramide and transmembrane signalling in enterocytes: Calcium response induced by HIV-1 surface-envelope glycoprotein gp120

Summary

Intracellular Ca2+ concentrations ([Ca2+]i) were measured in single-cultured human epithelial intestinal HT-29-D4 cells by digital microscopy using the Ca2+-sensitive fluorescent dye Fura-2. Exposure of these cells to HIV-1 surface-envelope glycoprotein gp120, or to a soluble form of its precursor (gp160), resulted in a significant, dose-dependent rise in [Ca2+]i. gp120 or gp160 specifically abrogated the [Ca2+]i response to the neuropeptide agonist neurotensin, which is a stimulator of chloride secretion via inositol trisphosphate-mediated Ca2+ mobilization. By contrast, upon exposure to neurotensin gp120 failed to show any increase in [Ca2+]i within the same cells, suggesting that both neurotensin and gp120 stimulate a common pathway of [Ca2+]i mobilization. gp120-/gp160-induced [Ca2+]i responses were abolished by preincubation with neutralizing antibodies directed against the third variable domain of gp120. These antibodies inhibited the binding of gp120/gp160 to galactosylceramide (GalCer), the alternative HIV-1 receptor in HT-29-D4 cells. Furthermore, HT-29-D4 cells displayed an important increase in [Ca2+]i to anti-GalCer mAb alone, which rendered the cells insensitive to gp120. By contrast, HT-29-D4 cells became insensitive to anti-GalCer mAb after exposure to gp120. These data indicate that HIV-1 may directly alter enterocytic functions through interaction with the GalCer receptor.

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Correspondence to Govindan Dayanithi.

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Dayanithi, G., Yahi, N., Baghdiguian, S. et al. Galactosylceramide and transmembrane signalling in enterocytes: Calcium response induced by HIV-1 surface-envelope glycoprotein gp120. Perspectives in Drug Discovery and Design 5, 181–191 (1996). https://doi.org/10.1007/BF02174013

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Keywords

  • Polymer
  • Calcium
  • Chloride
  • Inositol
  • Soluble Form