1. Biochemistry and Chemical Biology
  2. Cell Biology
Download icon

Regulation by the quorum sensor from Vibrio indicates a receptor function for the membrane anchors of adenylate cyclases

  1. Stephanie Beltz
  2. Jens Bassler
  3. Joachim E Schultz  Is a corresponding author
  1. Pharmazeutisches Institut der Universität Tübingen, Germany
  2. Max-Planck-Institut für Entwicklungsbiologie, Germany
Research Article
  • Cited 12
  • Views 1,815
  • Annotations
Cite this article as: eLife 2016;5:e13098 doi: 10.7554/eLife.13098

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.

Article and author information

Author details

  1. Stephanie Beltz

    Pharmazeutisches Institut der Universität Tübingen, Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.

  2. Jens Bassler

    Max-Planck-Institut für Entwicklungsbiologie, Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.

  3. Joachim E Schultz

    Pharmazeutisches Institut der Universität Tübingen, Tübingen, Germany
    For correspondence
    joachim.schultz@uni-tuebingen.de
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Michael A Marletta, University of California, Berkeley, United States

Publication history

  1. Received: November 17, 2015
  2. Accepted: February 26, 2016
  3. Accepted Manuscript published: February 27, 2016 (version 1)
  4. Version of Record published: March 29, 2016 (version 2)
  5. Version of Record updated: February 8, 2017 (version 3)

Copyright

© 2016, Beltz et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,815
    Page views
  • 327
    Downloads
  • 12
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Categories and tags

Further reading

    1. Biochemistry and Chemical Biology
    2. Medicine

    The half-life of the bone-derived hormone osteocalcin is regulated through O-glycosylation in mice, but not in humans

    Omar Al Rifai et al.
    Research Article Updated

    Osteocalcin (OCN) is an osteoblast-derived hormone with pleiotropic physiological functions. Like many peptide hormones, OCN is subjected to post-translational modifications (PTMs) which control its activity. Here, we uncover O-glycosylation as a novel PTM present on mouse OCN and occurring on a single serine (S8) independently of its carboxylation and endoproteolysis, two other PTMs regulating this hormone. We also show that O-glycosylation increases OCN half-life in plasma ex vivo and in the circulation in vivo. Remarkably, in human OCN (hOCN), the residue corresponding to S8 is a tyrosine (Y12), which is not O-glycosylated. Yet, the Y12S mutation is sufficient to O-glycosylate hOCN and to increase its half-life in plasma compared to wildtype hOCN. These findings reveal an important species difference in OCN regulation, which may explain why serum concentrations of OCN are higher in mouse than in human.

    1. Biochemistry and Chemical Biology
    2. Medicine

    Bone Hormones: Survival of the glycosylated

    Harry C Blair, Paul H Schlesinger
    Insight

    Osteocalcin is a bone matrix protein that acts like a hormone when it reaches the blood, and has different effects in mice and humans.

    1. Biochemistry and Chemical Biology

    Chemical genetics and proteome-wide site mapping reveal cysteine MARylation by PARP-7 on immune-relevant protein targets

    Kelsie M Rodriguez et al.
    Research Article

    Poly(ADP-ribose) polymerase 7 (PARP-7) has emerged as a critically important member of a large enzyme family that catalyzes ADP-ribosylation in mammalian cells. PARP-7 is a critical regulator of the innate immune response. What remains unclear is the mechanism by which PARP-7 regulates this process, namely because the protein targets of PARP-7 mono-ADP-ribosylation (MARylation) are largely unknown. Here, we combine chemical genetics, proximity labeling, and proteome-wide amino acid ADP-ribosylation site profiling for identifying the direct targets and sites of PARP-7-mediated MARylation in a cellular context. We found that the inactive PARP family member, PARP-13—a critical regulator of the antiviral innate immune response—is a major target of PARP-7. PARP-13 is preferentially MARylated on cysteine residues in its RNA binding zinc finger domain. Proteome-wide ADP-ribosylation analysis reveals cysteine as a major MARylation acceptor of PARP-7. This study provides insight into PARP-7 targeting and MARylation site preference.