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Biology subjects

Galant, S.

Publications and source records attributed to Galant, S..

2 recordsLinked to original sources

Natural genetic variation spans all predicted Rh5/Rh6 expression phenotypes in Drosophila R8 photoreceptors

Standing genetic variation is immediately available to selection, but how broad a range of phenotypes it can produce remains unknown for many traits. Here we address this question using the mutually exclusive Rhodopsin 5 (Rh5) and Rhodopsin 6 (Rh6) expression pattern in Drosophila R8 photoreceptors, a neuronal differentiation readout that permits enumeration of a finite set of predicted qualitative phenotypic changes. Wild flies and wild-derived inbred lines from the Drosophila Genome Reference Panel 2 (DGRP2) showed extensive variation in Rh5/Rh6 expression, including shifts in the relative abundance of Rh5- and Rh6-expressing R8s, Rh5/Rh6 co-expression, and loss of Rh5 or Rh6. Among 205 DGRP2 lines, we observed examples spanning all eight predicted qualitative phenotype categories. We also identified causal coding and regulatory variants, including alleles of sevenless, Rh5 and Rh6, and an intronic deletion in melted. These results show that standing natural variation can span the full predicted range of qualitative phenotypes in this system.

genetics↗

Physical interaction with Ephrin B1 promotes CXCR4 intracellular localization and oncogenic potential

Chemokine receptor 4 (CXCR4) is a member of the chemokine receptor exclusively activated by the chemokine CXCL12. While CXCR4 regulates numerous physiological processes associated with cell migration and embryogenesis, its overexpression has been involved in various cancer types. Studies suggest that intracellular CXCR4 expression rather than CXCR4-operated signaling underlies its pro-tumorigenic functions. Given the role of GPCR interacting proteins in their trafficking and subcellular localization, we characterized the CXCR4 interactome using an affinity purification coupled to mass spectrometry (AP-MS) strategy. The most abundant protein identified in the CXCR4 interactome is Ephrin B1, a member of the Ephrin protein family that shares several functions with CXCR4, such as the regulation of cell migration and proliferation. Further studies showed that interaction between CXCR4 and Ephrin B1 is direct and enhanced by treating cell with CXCL12. They also indicated that Ephrin B1 prevents CXCR4 N-glycosylation, decreases CXCR4 cell surface expression and consistently inhibits CXCL12-induced CXCR4 coupling to Gi1-3 and the recruitment of {beta}-arrestins 1 and 2. Conversely, Ephrin B1 signals to Erk1,2 through CXCR4 activation and mediates the decrease in Death Receptor 5 expression elicited by intracellular CXCR4. Collectively, these findings identify Ephrin B1 as a key mediator of CXCR4 tumorigenic signaling.

biochemistry↗