The LH/CG receptor activates canonical signaling pathway when expressed in Drosophila

Graves, J., Markman, S., Alegranti, Y., Gechtler, J., Johnson, R. I., Cagan, R. and Ben-Menahem, D. (2015) The LH/CG receptor activates canonical signaling pathway when expressed in Drosophila. Molecular and Cellular Endocrinology, 413, pp. 145-156. (doi: 10.1016/j.mce.2015.06.020) (PMID:26112185)

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Abstract

G-protein coupled receptors (GPCRs) and their ligands provide precise tissue regulation and are therefore often restricted to specific animal phyla. For example, the gonadotropins and their receptors are crucial for vertebrate reproduction but absent from invertebrates. In mammals, LHR mainly couples to the PKA signaling pathway, and CREB is the major transcription factor of this pathway. Here we present the results of expressing elements of the human gonadotropin system in Drosophila. Specifically, we generated transgenic Drosophila expressing the human LH/CG receptor (denoted as LHR), a constitutively active form of LHR, and an hCG analog. We demonstrate activation-dependent signaling by LHR to direct Drosophila phenotypes including lethality and specific midline defects; these phenotypes were due to LHR activation of PKA/CREB pathway activity. That the LHR can act in an invertebrate demonstrates the conservation of factors required for GPCR function among phylogenetically distant organisms. This novel gonadotropin model may assist the identification of new modulators of mammalian fertility by exploiting the powerful genetic and pharmacological tools available in Drosophila.

Item Type:Articles
Additional Information:This work was supported in part by a grant from the Faculty of Health Sciences, Ben-Gurion University of the Negev.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cagan, Professor Ross
Authors: Graves, J., Markman, S., Alegranti, Y., Gechtler, J., Johnson, R. I., Cagan, R., and Ben-Menahem, D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Molecular and Cellular Endocrinology
Publisher:Elsevier
ISSN:0303-7207
ISSN (Online):1872-8057
Published Online:23 June 2015

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