PUBLICATION
Cxcl12 evolution - subfunctionalization of a ligand through altered interaction with the chemokine receptor
- Authors
- Boldajipour, B., Doitsidou, M., Tarbashevich, K., Laguri, C., Yu, S.R., Ries, J., Dumstrei, K., Thelen, S., Dörries, J., Messerschmidt, E.M., Thelen, M., Schwille, P., Brand, M., Lortat-Jacob, H., and Raz, E.
- ID
- ZDB-PUB-110629-29
- Date
- 2011
- Source
- Development (Cambridge, England) 138(14): 2909-2914 (Journal)
- Registered Authors
- Boldajipour, Bijan, Brand, Michael, Doitsidou, Maria, Dörries, Julia, Dumstrei, Karin, Messerschmidt, Esther-Maria, Raz, Erez, Tarbashevich, Katsiyarina, Yu, Rachel Shuizi
- Keywords
- cxcr4, cell migration, chemokine, evolution, germ cell, zebrafish
- MeSH Terms
-
- Amino Acid Substitution
- Animals
- Cell Line
- Cell Movement/physiology*
- Chemokine CXCL12/genetics
- Chemokine CXCL12/metabolism*
- Evolution, Molecular*
- Gene Knockdown Techniques
- Germ Cells/physiology*
- Humans
- In Situ Hybridization
- Microscopy, Confocal
- Receptors, CXCR4/metabolism*
- Spectrometry, Fluorescence
- Zebrafish/embryology*
- Zebrafish/metabolism
- PubMed
- 21693511 Full text @ Development
Citation
Boldajipour, B., Doitsidou, M., Tarbashevich, K., Laguri, C., Yu, S.R., Ries, J., Dumstrei, K., Thelen, S., Dörries, J., Messerschmidt, E.M., Thelen, M., Schwille, P., Brand, M., Lortat-Jacob, H., and Raz, E. (2011) Cxcl12 evolution - subfunctionalization of a ligand through altered interaction with the chemokine receptor. Development (Cambridge, England). 138(14):2909-2914.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping