A splice variant of the G protein β3-subunit implicated in disease states does not modulate ion channels

Victor Ruiz-Velasco, Stephen R. Ikeda

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

A single-nucleotide polymorphism (C825T) in the GNB3 gene produces an alternative splice variant of the helerotrimeric G protein β3 subunit (Gβ3). Translation of the alternatively spliced mRNA results in a protein product, Gβ3-s, in which 41 amino acids are deleted from Gβ3. Interestingly, previous studies indicate that the C825T allele occurs with a high frequency in patients with certain vascular disorders. However, little information is available regarding the functional role Gβ3-s might play in ion channel modulation. To examine this aspect, Gβ3 or Gβ3-s, along with either Gγ2 or Gγ5, were expressed in rat sympathetic neurons by nuclear microinjection of vector encoding the desired protein. In contrast to Gβ3, expression of Gβ3-s did not modulate N-type Ca2+ or G protein-gated inwardly rectifying K+ channels. In addition, Gβ3-s did not appear to complex with a pertussis toxin-insensitive mutant of Gαi2 or couple to natively expressed α 2-adrenergic receptors. Finally, fluorescence resonance energy transfer (FRET) measurements indicated that enhanced yellow fluorescent protein (EYFP)-labeled Gβ3-s does not form a Gβγ heterodimer when coexpressed with enhanced cyan fluorescent protein (ECFP)-labeled Gγ2. Therefore, when expressed in sympathetic neurons, Gβ3-s appears to lack biological activity-hence pathological conditions in patients carrying the homozygous C825T allele may result from a functional knockout of Gβ3.

Original languageEnglish (US)
Pages (from-to)85-95
Number of pages11
JournalPhysiological genomics
Volume13
DOIs
StatePublished - Jul 2003

All Science Journal Classification (ASJC) codes

  • Physiology
  • Genetics

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