Different beta-subunits determine G-protein interaction with transmembrane receptors

Nature. 1992 Jul 30;358(6385):424-6. doi: 10.1038/358424a0.

Abstract

Regulatory GTP-binding proteins (G proteins) are membrane-attached heterotrimers (alpha, beta, gamma) that mediate cellular responses to a wide variety of extracellular stimuli. They undergo a cycle of guanine-nucleotide exchange and GTP hydrolysis, during which they dissociate into alpha-subunit and beta gamma complex. The roles of G-protein alpha-subunits in these processes and for the specificity of signal transduction are largely established; the beta- and gamma-subunits are essential for receptor-induced G-protein activation and seem to be less diverse and less specific. Although the complementary DNAs for several beta-subunits have been cloned, isolated subunits have only been studied as beta gamma complexes. Functional differences have been ascribed to the gamma-subunit on the basis of extensive sequence similarity among beta-subunits and apparent heterogeneity in gamma-subunit sequences. Beta gamma complexes can interact directly or indirectly with different effectors. They seem to be interchangeable in their interaction with pertussis toxin-sensitive alpha-subunits, so we tested this by microinjecting antisense oligonucleotides into nuclei of a rat pituitary cell line to suppress the synthesis of individual beta-subunits selectively. Here we show that two out of four subtypes of beta-subunits tested (beta 1 and beta 3) are selectively involved in the signal transduction cascades from muscarinic M4 (ref. 4) and somatostatin receptors, respectively, to voltage-dependent Ca2+ channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Calcium / physiology
  • Calcium Channels / physiology*
  • Cell Line
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / physiology*
  • Gene Expression
  • In Vitro Techniques
  • Ion Channel Gating
  • Macromolecular Substances
  • Molecular Sequence Data
  • Oligonucleotides, Antisense
  • RNA, Messenger / genetics
  • Rats
  • Receptors, Cell Surface / physiology*
  • Receptors, Muscarinic / physiology
  • Receptors, Neurotransmitter / physiology
  • Receptors, Somatostatin
  • Signal Transduction
  • Structure-Activity Relationship

Substances

  • Calcium Channels
  • Macromolecular Substances
  • Oligonucleotides, Antisense
  • RNA, Messenger
  • Receptors, Cell Surface
  • Receptors, Muscarinic
  • Receptors, Neurotransmitter
  • Receptors, Somatostatin
  • GTP-Binding Proteins
  • Calcium