The packing density of a supramolecular membrane protein cluster is controlled by cytoplasmic interactions

Abstract

Molecule clustering is an important mechanism underlying cellular self-organization. In the cell membrane, a variety of fundamentally different mechanisms drive membrane protein clustering into nanometre-sized assemblies. To date, it is unknown whether this clustering process can be dissected into steps differentially regulated by independent mechanisms. Using clustered syntaxin molecules as an example, we study the influence of a cytoplasmic protein domain on the clustering behaviour. Analysing protein mobility, cluster size and accessibility to myc-epitopes we show that forces acting on the transmembrane segment produce loose-clusters, while cytoplasmic protein interactions mediate a tightly packed state. We conclude that the data identify a hierarchy in membrane protein clustering likely being a paradigm for many cellular self-organization processes.

Article and author information

Author details

  1. Elisa Merklinger

    Membrane Biochemistry, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Jan-Gero Schloetel

    Membrane Biochemistry, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Pascal Weber

    Membrane Biochemistry, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Helena Batoulis

    Membrane Biochemistry, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Sarah Holz

    Membrane Biochemistry, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Nora Karnowski

    Chemical Biology, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Jérôme Finke

    Membrane Biochemistry, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Thorsten Lang

    Membrane Biochemistry, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany
    For correspondence
    thorsten.lang@uni-bonn.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9128-0137

Funding

Deutsche Forschungsgemeinschaft (TRR83 to T.L.)

  • Thorsten Lang

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Reinhard Jahn, Max Planck Institute for Biophysical Chemistry, Germany

Publication history

  1. Received: August 16, 2016
  2. Accepted: July 17, 2017
  3. Accepted Manuscript published: July 19, 2017 (version 1)
  4. Version of Record published: July 31, 2017 (version 2)

Copyright

© 2017, Merklinger 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.

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  1. Elisa Merklinger
  2. Jan-Gero Schloetel
  3. Pascal Weber
  4. Helena Batoulis
  5. Sarah Holz
  6. Nora Karnowski
  7. Jérôme Finke
  8. Thorsten Lang
(2017)
The packing density of a supramolecular membrane protein cluster is controlled by cytoplasmic interactions
eLife 6:e20705.
https://doi.org/10.7554/eLife.20705

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    Background:

    Few studies have assessed the role of individual plasma cholesterol levels in the association between egg consumption and the risk of cardiovascular diseases. This research aims to simultaneously explore the associations of self-reported egg consumption with plasma metabolic markers and these markers with the risk of cardiovascular disease (CVD).

    Methods:

    Totally 4778 participants (3401 CVD cases subdivided into subtypes and 1377 controls) aged 30–79 were selected based on the China Kadoorie Biobank. Targeted nuclear magnetic resonance was used to quantify 225 metabolites in baseline plasma samples. Linear regression was conducted to assess associations between self-reported egg consumption and metabolic markers, which were further compared with associations between metabolic markers and CVD risk.

    Results:

    Egg consumption was associated with 24 out of 225 markers, including positive associations for apolipoprotein A1, acetate, mean HDL diameter, and lipid profiles of very large and large HDL, and inverse associations for total cholesterol and cholesterol esters in small VLDL. Among these 24 markers, 14 were associated with CVD risk. In general, the associations of egg consumption with metabolic markers and of these markers with CVD risk showed opposite patterns.

    Conclusions:

    In the Chinese population, egg consumption is associated with several metabolic markers, which may partially explain the protective effect of moderate egg consumption on CVD.

    Funding:

    This work was supported by the National Natural Science Foundation of China (81973125, 81941018, 91846303, 91843302). The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants (2016YFC0900500, 2016YFC0900501, 2016YFC0900504, 2016YFC1303904) from the National Key R&D Program of China, National Natural Science Foundation of China (81390540, 81390541, 81390544), and Chinese Ministry of Science and Technology (2011BAI09B01). The funders had no role in the study design, data collection, data analysis and interpretation, writing of the report, or the decision to submit the article for publication.