TY - JOUR
T1 - The LH/CG receptor activates canonical signaling pathway when expressed in Drosophila
AU - Graves, Justin
AU - Markman, Svetlana
AU - Alegranti, Yair
AU - Gechtler, Jenia
AU - Johnson, Ruth I.
AU - Cagan, Ross
AU - Ben-Menahem, David
N1 - Publisher Copyright:
© 2015 Elsevier Ireland Ltd.
PY - 2015/9/5
Y1 - 2015/9/5
N2 - 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.
AB - 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.
KW - Gonadotropin evolution
KW - LHR
KW - Protein kinase A (PKA)
KW - cAMP response element-binding protein (CREB)
UR - http://www.scopus.com/inward/record.url?scp=84938288425&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2015.06.020
DO - 10.1016/j.mce.2015.06.020
M3 - Article
AN - SCOPUS:84938288425
SN - 0303-7207
VL - 413
SP - 145
EP - 156
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
ER -