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Alternative splicing directs the expression of two D2 dopamine receptor isoforms

Naturevolume 342, pages923–926 (1989)Cite this article

Abstract

DOPAMINE receptors are classified into Dl and D2 subtypes on the basis of their pharmacological properties and the intracellular responses they mediate1. The cerebral D2 dopamine receptor is the target of drugs used to alleviate the main symptoms of schizophrenia2–4. Although it is considered to be a single molecular entity, there is evidence that multiple D2-receptor subtypes exist5,6. A complementary DNA encoding a D2 receptor has recently been cloned7 and the deduced 415-amino-acid sequence indicates that it belongs to the large superfamily of receptors coupled to G proteins, and that its topology consists of seven transmembrane domains. In this family, the genes are frequently without introns and each is believed to encode a unique polypeptide product. Here we show that the gene for the D2 receptor produces two receptor isoforms by alternative messenger RNA splicing, providing a route to receptor diversity in this family. One isoform corresponds to the D2(415) receptor7, but the second contains an additional sequence encoding a 29-amino-acid fragment, defining a novel D2(444) receptor isoform. Expression of the two isoforms is tissue-specific, and both are regulated by guanyl nucleotides. As the extra sequence is located within a putative cytoplasmic loop that binds to G proteins, the two isoforms might interact with different G proteins and thereby initiate distinct intracellular signals.

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Author information

Authors and Affiliations

  1. Unité de Neurobiologie et Pharmacologie, U. 109 de I'lnserm, Centre Paul Broca, 2 ter, rue d'Alésia, 75014, Paris, France

    Bruno Giros, Pierre Sokoloff, Marie-Pascale Martres, Jean-François Riou & Jean-Charles Schwartz

  2. Laboratoire de Physiologie, Faculté de Pharmacie,Université René Descartes, Paris, France

    Jean-François Riou

  3. Laboratoire de Biologie Moléculaire des Récepteurs, CNRS et institut Pasteur, 25 rue du Docteur Roux, 75724, Paris, Cedex 15, France

    Laurent J. Emorine

Authors
  1. Bruno Giros

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  2. Pierre Sokoloff

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  3. Marie-Pascale Martres

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  4. Jean-François Riou

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  5. Laurent J. Emorine

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  6. Jean-Charles Schwartz

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Giros, B., Sokoloff, P., Martres, MP.et al. Alternative splicing directs the expression of two D2 dopamine receptor isoforms.Nature342, 923–926 (1989). https://doi.org/10.1038/342923a0

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