A Cellular System for Spatial Signal Decoding in Chemical Gradients

被引:36
作者
Hegemann, Bjoern [1 ]
Unger, Michael [1 ,2 ]
Lee, Sung Sik [1 ]
Stoffel-Studer, Ingrid [1 ]
van den Heuvel, Jasmin [1 ]
Pelet, Serge [3 ]
Koeppl, Heinz [2 ,4 ]
Peter, Matthias [1 ]
机构
[1] ETH, Inst Biochem, Dept Biol, CH-8093 Zurich, Switzerland
[2] ETH, Automat Control Lab, CH-8092 Zurich, Switzerland
[3] Univ Lausanne, Dept Fundamental Microbiol, CH-1015 Lausanne, Switzerland
[4] Tech Univ Darmstadt, Dept Elect Engn & Informat Technol, D-64283 Darmstadt, Germany
基金
欧洲研究理事会; 瑞士国家科学基金会;
关键词
EXCHANGE FACTOR CDC24P; SACCHAROMYCES-CEREVISIAE; ACTIN CYTOSKELETON; IMAGE-ANALYSIS; POLARITY; YEAST; POLARIZATION; CHEMOTAXIS; PROTEINS; KINASE;
D O I
10.1016/j.devcel.2015.10.013
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:458 / 470
页数:13
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  • [1] UNC-6/Netrin induces neuronal asymmetry and defines the site of axon formation
    Adler, CE
    Fetter, RD
    Bargmann, CI
    [J]. NATURE NEUROSCIENCE, 2006, 9 (04) : 511 - 518
  • [2] Chemical Gradients and Chemotropism in Yeast
    Arkowitz, Robert A.
    [J]. COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY, 2009, 1 (02): : a001958
  • [3] A role for the yeast actin cytoskeleton in pheromone receptor clustering and signalling
    Ayscough, KR
    Drubin, DG
    [J]. CURRENT BIOLOGY, 1998, 8 (16) : 927 - 930
  • [4] Bendezu F. O., 2012, CURR BIOL, V23, P1
  • [5] Cellular responses to extracellular guidance cues
    Berzat, Anastacia
    Hall, Alan
    [J]. EMBO JOURNAL, 2010, 29 (16) : 2734 - 2745
  • [6] A chemical switch for inhibitor-sensitive alleles of any protein kinase
    Bishop, AC
    Ubersax, JA
    Petsch, DT
    Matheos, DP
    Gray, NS
    Blethrow, J
    Shimizu, E
    Tsien, JZ
    Schultz, PG
    Rose, MD
    Wood, JL
    Morgan, DO
    Shokat, KM
    [J]. NATURE, 2000, 407 (6802) : 395 - 401
  • [7] Nuclear export of Far1p in response to pheromones requires the export receptor Msn5p/Ste21p
    Blondel, M
    Alepuz, PM
    Huang, LS
    Shaham, S
    Ammerer, G
    Peter, M
    [J]. GENES & DEVELOPMENT, 1999, 13 (17) : 2284 - 2300
  • [8] Assembly of scaffold-mediated complexes containing Cdc42p, the exchange factor Cdc24p and the effector Cla4p required for cell cycle-regulated phosphorylation of Cdc24p
    Bose, I
    Irazoqui, JE
    Moskow, JJ
    Bardes, ESG
    Zyla, TR
    Lew, DJ
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (10) : 7176 - 7186
  • [9] Brachmann CB, 1998, YEAST, V14, P115
  • [10] A positive feedback loop stabilizes the guanine-nucleotide exchange factor Cdc24 at sites of polarization
    Butty, AC
    Perrinjaquet, N
    Petit, A
    Jaquenoud, M
    Segall, JE
    Hofmann, K
    Zwahlen, C
    Peter, M
    [J]. EMBO JOURNAL, 2002, 21 (07) : 1565 - 1576