A Cellular System for Spatial Signal Decoding in Chemical Gradients

Björn Hegemann; Michael Unger; Sung Sik Lee; Ingrid Stoffel-Studer; Jasmin van den Heuvel; Serge Pelet; Heinz Koeppl; Matthias Peter

doi:10.1016/j.devcel.2015.10.013

A Cellular System for Spatial Signal Decoding in Chemical Gradients

Dev Cell. 2015 Nov 23;35(4):458-70. doi: 10.1016/j.devcel.2015.10.013. Epub 2015 Nov 12.

Authors

Björn Hegemann¹, Michael Unger², Sung Sik Lee³, Ingrid Stoffel-Studer³, Jasmin van den Heuvel³, Serge Pelet⁴, Heinz Koeppl⁵, Matthias Peter⁶

Affiliations

¹ Department of Biology, Institute of Biochemistry, ETH Zurich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland. Electronic address: bjoern.hegemann@bc.biol.ethz.ch.
² Department of Biology, Institute of Biochemistry, ETH Zurich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland; Automatic Control Laboratory, ETH Zurich, Physikstrasse 3, 8092 Zürich, Switzerland.
³ Department of Biology, Institute of Biochemistry, ETH Zurich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland.
⁴ Department of Fundamental Microbiology, University of Lausanne, Biophore Building, 1015 Lausanne, Switzerland.
⁵ Automatic Control Laboratory, ETH Zurich, Physikstrasse 3, 8092 Zürich, Switzerland; Department of Electrical Engineering and Information Technology, Technische Universität Darmstadt, Rundeturmstrasse 12, 64283 Darmstadt, Germany.
⁶ Department of Biology, Institute of Biochemistry, ETH Zurich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland. Electronic address: matthias.peter@bc.biol.ethz.ch.

PMID: 26585298
DOI: 10.1016/j.devcel.2015.10.013

Abstract

Directional cell growth requires that cells read and interpret shallow chemical gradients, but how the gradient directional information is identified remains elusive. We use single-cell analysis and mathematical modeling to define the cellular gradient decoding network in yeast. Our results demonstrate that the spatial information of the gradient signal is read locally within the polarity site complex using double-positive feedback between the GTPase Cdc42 and trafficking of the receptor Ste2. Spatial decoding critically depends on low Cdc42 activity, which is maintained by the MAPK Fus3 through sequestration of the Cdc42 activator Cdc24. Deregulated Cdc42 or Ste2 trafficking prevents gradient decoding and leads to mis-oriented growth. Our work discovers how a conserved set of components assembles a network integrating signal intensity and directionality to decode the spatial information contained in chemical gradients.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Polarity / physiology*
Chemotaxis
Image Processing, Computer-Assisted
Immunoblotting
Microfluidic Analytical Techniques
Mitogen-Activated Protein Kinases / genetics
Mitogen-Activated Protein Kinases / metabolism*
Models, Theoretical
Protein Binding
Protein Transport
Receptors, Mating Factor / genetics
Receptors, Mating Factor / metabolism*
Saccharomyces cerevisiae / genetics
Saccharomyces cerevisiae / growth & development*
Saccharomyces cerevisiae / metabolism*
Saccharomyces cerevisiae Proteins / genetics
Saccharomyces cerevisiae Proteins / metabolism*
Signal Transduction*
Single-Cell Analysis / methods
cdc42 GTP-Binding Protein, Saccharomyces cerevisiae / genetics
cdc42 GTP-Binding Protein, Saccharomyces cerevisiae / metabolism*

Substances

Receptors, Mating Factor
STE2 protein, S cerevisiae
Saccharomyces cerevisiae Proteins
FUS3 protein, S cerevisiae
Mitogen-Activated Protein Kinases
cdc42 GTP-Binding Protein, Saccharomyces cerevisiae