Rxivist logo

Gsα stimulation of mammalian adenylate cyclases regulated by their hexahelical membrane anchors

By Anubha Seth, Manuel Finkbeiner, Julia Grischin, Joachim E. Schultz

Posted 06 Jul 2019
bioRxiv DOI: 10.1101/694877 (published DOI: 10.1016/j.cellsig.2020.109538)

Mammalian adenylate cyclases (ACs) are pseudoheterodimers with dissimilar hexahelical membrane-anchors, isoform-specifically conserved for more than half a billion years. We exchanged both membrane anchors of the AC isoform 2 by the isosteric quorum-sensing receptor from Vibrio , CqsS, which has a ligand, Cholera -Autoinducer-1 (CAI-1). In the chimera, AC activity was stimulated by Gsα, CAI-1 had no effect. Surprisingly, CAI-1 inhibited Gsα stimulation. We report that Gsα stimulation of human AC isoforms 2, 3, 5, and 9 expressed in Sf9 cells is inhibited by serum as is AC activity in membranes from rat brain cortex. AC2 activation by forskolin or forskolin/Gsα was similarly inhibited. Obviously, serum contains as yet unidentified factors affecting AC activity. The data establish a linkage in ACs, in which the membrane anchors, as receptors, transduce extracellular signals to the cytosolic catalytic dimer. A mechanistic three state model of AC regulation is presented compatible with all known regulatory inputs into mammalian ACs. The data allow designating the membrane anchors of mammalian ACs as orphan receptors and establish a new level of AC regulation.

Download data

  • Downloaded 192 times
  • Download rankings, all-time:
    • Site-wide: 72,656 out of 92,062
    • In biochemistry: 2,301 out of 3,096
  • Year to date:
    • Site-wide: 58,280 out of 92,062
  • Since beginning of last month:
    • Site-wide: 59,771 out of 92,062

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


PanLingua

Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News