Journal article

Cxcl12 evolution – subfunctionalization of a ligand through altered interaction with the chemokine receptor

  • Boldajipour, Bijan Institute of Cell Biology, Center of Molecular Biology of Inflammation, University of Münster, Münster, Germany - Max-Planck Institute of Biophysical Chemistry, Göttingen, Germany
  • Doitsidou, Maria Max-Planck Institute of Biophysical Chemistry, Göttingen, Germany
  • Tarbashevich, Katsiaryna Institute of Cell Biology, Center of Molecular Biology of Inflammation, University of Münster, Münster, Germany
  • Laguri, Cedric IBS, Institut de Biologie Structurale, UMR 5075 CNRS CEA UJF, Grenoble, France
  • Yu, Shuizi Rachel Biotechnology Center, and Center for Regenerative Therapies, Dresden, Germany
  • Ries, Jonas Biophysics, Biotechnology Center, Dresden, Germany
  • Dumstrei, Karin Max-Planck Institute of Biophysical Chemistry, Göttingen, Germany
  • Thelen, Sylvia Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Dörries, Julia Max-Planck Institute of Biophysical Chemistry, Göttingen, Germany
  • Messerschmidt, Esther-Maria Institute of Cell Biology, Center of Molecular Biology of Inflammation, University of Münster, Münster, Germany
  • Thelen, Marcus Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Schwille, Petra Biophysics, Biotechnology Center, Dresden, Germany
  • Brand, Michael Biotechnology Center, and Center for Regenerative Therapies, Dresden, Germany
  • Lortat-Jacob, Hugues IBS, Institut de Biologie Structurale, UMR 5075 CNRS CEA UJF, Grenoble, France
  • Raz, Erez Institute of Cell Biology, Center of Molecular Biology of Inflammation, University of Münster, Münster, Germany - Max-Planck Institute of Biophysical Chemistry, Göttingen, Germany
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    21.06.2011
Published in:
  • Development. - 2011, vol. 138, no. 14, p. 2909-2914
English The active migration of primordial germ cells (PGCs) from their site of specification towards their target is a valuable model for investigating directed cell migration within the complex environment of the developing embryo. In several vertebrates, PGC migration is guided by Cxcl12, a member of the chemokine superfamily. Interestingly, two distinct Cxcl12 paralogs are expressed in zebrafish embryos and contribute to the chemotattractive landscape. Although this offers versatility in the use of chemokine signals, it also requires a mechanism through which migrating cells prioritize the relevant cues that they encounter. Here, we show that PGCs respond preferentially to one of the paralogs and define the molecular basis for this biased behavior. We find that a single amino acid exchange switches the relative affinity of the Cxcl12 ligands for one of the duplicated Cxcr4 receptors, thereby determining the functional specialization of each chemokine that elicits a distinct function in a distinct process. This scenario represents an example of protein subfunctionalization – the specialization of two gene copies to perform complementary functions following gene duplication – which in this case is based on receptor-ligand interaction. Such specialization increases the complexity and flexibility of chemokine signaling in controlling concurrent developmental processes.
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  • English
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Medicine
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https://susi.usi.ch/usi/documents/318805
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