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Article Dans Une Revue Development (Cambridge, England) Année : 2011

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

Bijan Boldajipour
  • Fonction : Auteur
Maria Doitsidou
  • Fonction : Auteur
Katsiaryna Tarbashevich
  • Fonction : Auteur
Cédric Laguri
Shuizi Rachel Yu
  • Fonction : Auteur
Jonas Ries
Karin Dumstrei
  • Fonction : Auteur
Sylvia Thelen
  • Fonction : Auteur
Julia Dörries
  • Fonction : Auteur
Esther-Maria Messerschmidt
  • Fonction : Auteur
Petra Schwille
  • Fonction : Auteur
Hugues Lortat-Jacob
  • Fonction : Auteur
  • PersonId : 970500
Erez Raz
  • Fonction : Auteur

Résumé

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.

Dates et versions

hal-00638476 , version 1 (04-11-2011)

Identifiants

Citer

Bijan Boldajipour, Maria Doitsidou, Katsiaryna Tarbashevich, Cédric Laguri, Shuizi Rachel Yu, et al.. Cxcl12 evolution--subfunctionalization of a ligand through altered interaction with the chemokine receptor.. Development (Cambridge, England), 2011, 138 (14), pp.2909-14. ⟨10.1242/dev.068379⟩. ⟨hal-00638476⟩
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