Intracellular retention of the two isoforms of the D(2) dopamine receptor promotes endoplasmic reticulum disruption. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Cell Science Année : 2001

Intracellular retention of the two isoforms of the D(2) dopamine receptor promotes endoplasmic reticulum disruption.

Résumé

The dopamine D(2) receptor exists as a long (D(2a)) and a short (D(2b)) isoform generated by alternative splicing of the corresponding transcript, which modifies the length of the third cytoplasmic loop implicated in heterotrimeric G-protein-coupling. Anatomical data suggested that this segment regulates the intracellular traffic and localization of the receptor. To directly address this question we used a combination of tagging procedures and immunocytochemical techniques to detect each of the two D(2) receptor isoforms. Surprisingly, most of the newly synthesized receptors accumulate in large intracellular compartments, the plasma membrane being only weakly labeled, without significant difference between the two receptor isoforms. Double labeling experiments showed that this localization corresponded neither to endosomal compartments nor to the Golgi apparatus. The D(2) receptor is mostly retained in the endoplasmic reticulum (ER), the long isoform more efficiently than the short one. It is accompanied by a striking vacuolization of the ER, roughly proportional to the expression levels of the two receptor isoforms. This phenomenon is partly overcome by treatment with pertussis toxin. In addition, an intrinsic activity of the D(2) receptor isoforms is revealed by [(35)S]-GTP gamma S binding and cAMP assay, which suggested that expression of weakly but constitutively active D(2) receptors promotes activation of heterotrimeric G protein inside the secretory pathway. This mechanism may participate in the regulation of the cellular traffic of the D(2) receptors isoforms.
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Dates et versions

hal-00122165 , version 1 (27-12-2006)

Identifiants

  • HAL Id : hal-00122165 , version 1
  • PUBMED : 11682611

Citer

Delphine Prou, W. J. Gu, Stéphane Le Crom, Jean-Didier Vincent, J. Salamero, et al.. Intracellular retention of the two isoforms of the D(2) dopamine receptor promotes endoplasmic reticulum disruption.. Journal of Cell Science, 2001, 114 (Pt 19), pp.3517-27. ⟨hal-00122165⟩

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