Cxcl12 evolution – subfunctionalization of a ligand through altered interaction with the chemokine receptor
| Autor: | Karin Dumstrei, Esther-Maria Messerschmidt, Julia Dörries, Maria Doitsidou, Hugues Lortat-Jacob, Bijan Boldajipour, Erez Raz, Petra Schwille, Marcus Thelen, Jonas Ries, Michael Brand, Sylvia Thelen, Katsiaryna Tarbashevich, Shuizi Rachel Yu, Cédric Laguri |
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| Přispěvatelé: | Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Theodor Kocher Institute, University of Bern, Biotechnology Center, and Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden = Dresden University of Technology (TU Dresden), ANR-05-BLAN-0271,CHEMOGLYCAN,STRUCTURAL AND FUNCTIONAL STUDIES OF SDF-1/CXCL12 INTERACTIONS WITH HEPARAN SULPHATE IN BOTH HOMEOSTASIS AND PATHOLOGY(2005), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2011 |
| Předmět: |
Chemokine
CXCR4 Chemokine receptor 0302 clinical medicine Cell Movement MESH: Microscopy Confocal MESH: Animals MESH: Cell Movement Zebrafish In Situ Hybridization MESH: Evolution Molecular Genetics 0303 health sciences Microscopy Confocal Cell migration MESH: Amino Acid Substitution Cell biology Gene Knockdown Techniques embryonic structures MESH: Chemokine CXCL12 MESH: Spectrometry Fluorescence Receptors CXCR4 Biology MESH: Receptors CXCR4 Cell Line Evolution Molecular 03 medical and health sciences MESH: In Situ Hybridization Specialization (functional) Animals Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology MESH: Zebrafish Molecular Biology 030304 developmental biology MESH: Humans biology.organism_classification MESH: Gene Knockdown Techniques Chemokine CXCL12 MESH: Cell Line MESH: Germ Cells Germ Cells Spectrometry Fluorescence Amino Acid Substitution biology.protein Subfunctionalization 030217 neurology & neurosurgery Function (biology) Developmental Biology |
| Zdroj: | Development Development (Cambridge, England) Development (Cambridge, England), 2011, 138 (14), pp.2909-14. ⟨10.1242/dev.068379⟩ Development (Cambridge, England), Company of Biologists, 2011, 138 (14), pp.2909-14. ⟨10.1242/dev.068379⟩ |
| ISSN: | 1477-9129 0950-1991 |
| DOI: | 10.1242/dev.068379 |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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