title: Chimeric GnRH-LH receptors and LH receptors lacking C-terminus palmitoylation sites do not localize to plasma membrane rafts.
abstract: Luteinizing hormone and gonadotropin releasing hormone receptors (LHR and GnRHR, respectively) are G protein-coupled receptors with important functions in reproduction. We have developed chimeric GnRHR-LHR that contain the full GnRHR coupled to various forms of the LH receptor C-terminus to explore the role of the LH receptor C-terminus in raft localization of the receptor and signaling. Addition of the full-length LHR C-terminus to GnRHR resulted in localization of the resting chimeric receptor in the bulk membrane rather than plasma membrane rafts as has been reported for the wild-type GnRHR [A. Navratil, S. Bliss, K. Berghorn, J. Haughian, T. Farmerie, J. Graham, C. Clay, M. Roberson, Constitutive localization of the gonadotropin-releasing hormone (GnRH) receptor to low density membrane microdomains is necessary for GnRH signaling to ERK, J. Biol. Chem. 278 (2003) 31593-31602]. With truncation of the LHR C-terminus, approximately 3% of chimeric receptors appeared in low density membrane fractions. Palmitoylation of sites on the LHR C-terminus appears important for raft localization. Mutations to C-terminus palmitoylation sites eliminated translocation of LH receptors from the bulk membrane to rafts upon binding of hCG although these mutant receptors retained the ability to signal via cAMP.
authors.affiliation: Cell and Molecular Biology Program, Colorado State University, Fort Collins, 80523, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lei
authors.forename: Guy M
authors.initials: GM
authors.lastname: Hagen
authors.forename: Steven M L
authors.initials: SM
authors.lastname: Smith
authors.forename: B George
authors.initials: BG
authors.lastname: Barisas
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Roess
mesh_terms: D000818:Animals; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism*; D017353:Gene Deletion; D010168:Palmitates / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D051381:Rats; D011974:Receptors, LH / Q000235:genetics / Q000378:metabolism*; D011966:Receptors, LHRH / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013395:Sucrose / Q000378:metabolism
chemical_list: D010168:Palmitates; D011974:Receptors, LH; D011966:Receptors, LHRH; D011993:Recombinant Fusion Proteins; D013395:Sucrose