A Mass Spectrometric-Derived Cell Surface Protein Atlas

April 20, 2015

Reference

Published: April 20, 2015 – http://dx.doi.org/10.1371/journal.pone.0121314 Cell surface proteins are major targets of biomedical research due to their utility as cellular markers and their extracellular accessibility for pharmacological intervention. However, information about the cell surface protein repertoire (the surfaceome) of individual cells is only sparsely available. Here, we applied the Cell Surface Capture (CSC) technology to 41 human and 31 mouse cell types to generate a mass-spectrometry derived Cell Surface Protein Atlas (CSPA) providing cellular surfaceome snapshots at high resolution. The CSPA is presented in form of an easy-to-navigate interactive database, a downloadable data matrix and with tools for targeted surfaceome rediscovery (http://wlab.ethz.ch/cspa).

Abstract

The cellular surfaceome snapshots of different cell types, including cancer cells, resulted in a combined dataset of 1492 human and 1296 mouse cell surface glycoproteins, providing experimental evidence for their cell surface expression on different cell types, including 136 G-protein coupled receptors and 75 membrane receptor tyrosine-protein kinases. Integrated analysis of the CSPA reveals that the concerted biological function of individual cell types is mainly guided by quantitative rather than qualitative surfaceome differences. The CSPA will be useful for the evaluation of drug targets, for the improved classification of cell types and for a better understanding of the surfaceome and its concerted biological functions in complex signaling microenvironments.

Author

Damaris Bausch-Fluck Affiliations Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland, Department of Health Sciences and Technology, BMPP, ETH Zurich, Zurich, Switzerland Andreas Hofmann Current Address: Novartis Institute of Biomedical Research, Novartis, Basel, Switzerland Affiliation Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland Thomas Bock Current Address: European Molecular Biology Laboratory, Heidelberg, Germany Affiliation Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland Andreas P. Frei Current Address: Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, California, United States of America Affiliation Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland Ferdinando Cerciello Current Address: James Thoracic Center, James Cancer Center, The Ohio State University Medical Center, Columbus, Ohio, United States of America Affiliations Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland, Laboratory of Molecular Oncology, University Hospital Zurich, Zurich, Switzerland Andrea Jacobs Current Address: Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland Affiliation Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland Hansjoerg Moest Current Address: Novartis Institute of Biomedical Research, Novartis, Basel, Switzerland Affiliation Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland Ulrich Omasits Affiliations Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland, Department of Health Sciences and Technology, BMPP, ETH Zurich, Zurich, Switzerland Rebekah L. Gundry Affiliation Department of Biochemistry, Medical College of Wisconsin, Wisconsin, Milwaukee, United States of America Charles Yoon Affiliation Institute for Biomaterials & Biomedical Engineering, University of Toronto, Toronto, Canada Ralph Schiess Current Address: ProteoMediX AG, Schlieren, Switzerland Affiliation Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland Alexander Schmidt Current Address: Proteomics Core Facility, Biozentrum, University of Basel, Basel, Switzerland Affiliation Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland Paulina Mirkowska Affiliations Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland, Oncology Research Laboratory, University Children Hospital Zurich, Zurich, Switzerland Anetta Härtlová Current Address: College of Life Sciences, University of Dundee, Dundee, United Kingdom Affiliation Centre of Advanced Studies, Faculty of Military Health Sciences, University of Defense, Hradec Kralove, Czech Republic Jennifer E. Van Eyk Current Address: Cedars-Sinai, Clinical Biosystem Research Institute, Los Angeles, California, United States of America Affiliation Department of Medicine, Biological Chemistry and Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America Jean-Pierre Bourquin Affiliation Oncology Research Laboratory, University Children Hospital Zurich, Zurich, Switzerland Ruedi Aebersold Affiliations Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland, Center for Systems Physiology and Metabolic Diseases, Zurich, Switzerland, Faculty of Science, University of Zurich, Zurich, Switzerland Kenneth R. Boheler Affiliations SCRMC, LKS Faculty of Medicine, Hong Kong University, Hong Kong, Hong Kong SAR, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America Peter Zandstra Affiliation Institute for Biomaterials & Biomedical Engineering, University of Toronto, Toronto, Canada Bernd Wollscheid * E-mail: wbernd@ethz.ch Affiliations Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland, Department of Health Sciences and Technology, BMPP, ETH Zurich, Zurich, Switzerland

Competing Interests

The authors have declared that no competing interests exist.

Author Contributions

Conceived and designed the experiments: DBF BW KRB PZ RA. Performed the experiments: DBF AH TB APF FC AJ HM RLG CY RS AS PM AH. Analyzed the data: DBF UO. Contributed reagents/materials/analysis tools: AS APF FC TB BW. Wrote the paper: DBF BW. Supervised experiments: JVE JPB.