Alternative splicing of the dopamine D2 receptor directs specificity of coupling to G-proteins. - Archive ouverte HAL Access content directly
Journal Articles Journal of Biological Chemistry Year : 1995

Alternative splicing of the dopamine D2 receptor directs specificity of coupling to G-proteins.

Abstract

Two isoforms of the dopamine D2 receptor have been characterized, D2L (long) and D2S (short), generated by alternative splicing from the same gene. They differ by an in-frame insert of 29 amino acids specific to D2L within the putative third intracytoplasmic loop of the receptor. We have previously demonstrated (Montmayeur, J.-P., Guiramand, J., and Borelli, E. (1993) Mol. Endocrinol. 7, 161-170) that D2S and D2L, although presenting very similar pharmacological profiles, couple differently to the alpha-subunit of guanine nucleotide-binding regulatory proteins (G-proteins). In particular, D2L, but not D2S, requires the presence of the alpha-subunit of the inhibitory G-protein (G alpha i2) to elicit greater inhibition of adenylyl cyclase activity. The insert present in D2L must therefore confer the specificity of interaction with G alpha i2. Thus, we introduced substitution mutations within the D2L insert. These mutant receptors were expressed in JEG3 cells, a G alpha i2-deficient cell line, scoring for those presenting an increased inhibition of adenylyl cyclase by dopamine. Our analysis identified two mutants, S259/262A and D249V, with these properties. These results clearly show that the insert present in D2L plays a critical role in the selectivity for the G-proteins interacting with the receptor.
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Dates and versions

hal-00422122 , version 1 (20-08-2019)

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Janique Guiramand, Jean-Pierre Montmayeur, Jocelyn Ceraline, M. Bhatia, Emiliana Borrelli. Alternative splicing of the dopamine D2 receptor directs specificity of coupling to G-proteins.. Journal of Biological Chemistry, 1995, 270 (13), pp.7354-7358. ⟨10.1074/jbc.270.13.7354⟩. ⟨hal-00422122⟩
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