G-protein-coupled receptor trafficking: understanding the chemical basis of health and disease.
The primary function of cell surface receptors is to recognize specific chemical signals from other substances and produce a biological response. Point mutations in cell surface receptors may result in production of misfolded proteins that are translated but do not reach their proper functional destination in the cell. Also, for some G-protein-coupled receptors, large amounts of wild-type receptor may be destroyed without arriving at the plasma membrane (PM). For the human gonadotropin-releasing hormone receptor, this "inefficiency" has resulted from strong and convergent evolutionary pressure, producing receptor molecules that are sensitive to single changes in chemical charge and are delicately balanced between expression at the PM or retention/degradation in the endoplasmic reticulum. This Perspective focuses on the evolved mechanisms that control PM expression of this receptor at this post-translational level.
Ulloa-Aguirre
Alfredo
A
Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon 97006, USA.
Janovick
Jo Ann
JA
Miranda
Alfredo Leaños
AL
Conn
P Michael
PM
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D019143:Evolution, Molecular; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D011966:Receptors, LHRH / Q000378:metabolism
D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D011966:Receptors, LHRH