title: Regulation by the quorum sensor from Vibrio indicates a receptor function for the membrane anchors of adenylate cyclases.
abstract: Adenylate cyclases convert intra- and extracellular stimuli into a second messenger cAMP signal. Many bacterial and most eukaryotic ACs possess membrane anchors with six transmembrane spans. We replaced the anchor of the AC Rv1625c by the quorum-sensing receptor from Vibrio harveyi which has an identical 6TM design and obtained an active, membrane-anchored AC. We show that a canonical class III AC is ligand-regulated in vitro and in vivo. At 10 µM, the cholera-autoinducer CAI-1 stimulates activity 4.8-fold. A sequence based clustering of membrane domains of class III ACs and quorum-sensing receptors established six groups of potential structural and functional similarities. The data support the notion that 6TM AC membrane domains may operate as receptors which directly regulate AC activity as opposed and in addition to the indirect regulation by GPCRs in eukaryotic congeners. This adds a completely novel dimension of potential AC regulation in bacteria and vertebrates.
authors.affiliation: Pharmazeutisches Institut der Universität Tübingen, Tübingen, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Beltz
authors.affiliation: Max-Planck-Institut für Entwicklungsbiologie, Tübingen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Bassler
authors.affiliation: Pharmazeutisches Institut der Universität Tübingen, Tübingen, Germany.
authors.forename: Joachim E
authors.identifier: http://orcid.org/0000-0002-1985-4853
authors.initials: JE
authors.lastname: Schultz
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics* / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D007659:Ketones / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000235:genetics; D053038:Quorum Sensing; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014733:Vibrio / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology
chemical_list: C525620:3-hydroxytridecan-4-one; D007659:Ketones; D011993:Recombinant Fusion Proteins; D000262:Adenylyl Cyclases
keywords: adenylate cyclase; biochemistry; cell biology; evolution; none; quorum-sensing receptor; vibrio