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Alternative splicing directs the expression of two D2 dopamine receptor isoforms
B Giros1, P Sokoloff, M P Martres
1Unité de Neurobiologie et Pharmacologie, U. 109 de l'inserm Centre Paul Broca, Paris, France.
Nature
|December 21, 1989
Summary
The D2 dopamine receptor gene produces two distinct isoforms through alternative splicing, leading to greater receptor diversity. These isoforms may interact with different G proteins, influencing intracellular signaling pathways.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Dopamine receptors, specifically D1 and D2 subtypes, mediate various intracellular responses.
- The D2 dopamine receptor is a key target for treating schizophrenia symptoms.
- While considered a single entity, evidence suggests multiple D2 receptor subtypes may exist.
Purpose of the Study:
- To investigate the molecular basis of potential D2 dopamine receptor diversity.
- To determine if the D2 receptor gene can produce multiple protein variants.
- To explore the implications of receptor diversity for intracellular signaling.
Main Methods:
- Cloning of complementary DNA encoding the D2 receptor.
- Analysis of messenger RNA (mRNA) splicing patterns.
- Expression studies of different receptor isoforms in tissues.
- Investigation of guanyl nucleotide regulation.
Main Results:
- The D2 receptor gene generates two distinct isoforms via alternative mRNA splicing: D2(415) and a novel D2(444) isoform.
- The D2(444) isoform contains an additional 29-amino-acid sequence compared to D2(415).
- Expression of these isoforms is tissue-specific and regulated by guanyl nucleotides.
Conclusions:
- Alternative splicing of the D2 receptor gene provides a mechanism for generating receptor diversity.
- The additional sequence in the D2(444) isoform, located in a G protein-binding domain, suggests differential G protein interaction.
- These findings indicate that D2 receptor isoforms may initiate distinct intracellular signals, impacting neuronal function.