title: Functional significance of cleavable signal peptides of G protein-coupled receptors.
abstract: About 5-10% of the G protein-coupled receptors (GPCRs) contain N-terminal signal peptides that are cleaved off by the signal peptidases of the endoplasmic reticulum (ER) during the translocon-mediated receptor insertion into the ER membrane. The reason as to why only a subset of the GPCRs requires these additional signal peptides was addressed in the past decade only by a limited number of studies. Recent progress suggests that signal peptides of GPCRs do not only serve the classical ER targeting and translocon gating functions as described for the signal peptides of secretory proteins. In the case of GPCRs, uncleaved pseudo signal peptides may regulate receptor expression at the plasma membrane and may also influence G protein coupling. Moreover, signal peptides of GPCRs seem to match functionally with sequences of the mature N tails. In this review, we summarize the current knowledge about cleavable signal peptides of GPCRs and address the question whether these sequences may be future drug targets in pharmacology.
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Str. 10, 13125 Berlin, Germany. schuelein@fmp-berlin.de
authors.forename: Ralf
authors.initials: R
authors.lastname: Schülein
authors.forename: Carolin
authors.initials: C
authors.lastname: Westendorf
authors.forename: Gerd
authors.initials: G
authors.lastname: Krause
authors.forename: Walter
authors.initials: W
authors.lastname: Rosenthal
mesh_terms: D000818:Animals; D006801:Humans; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D021382:Protein Sorting Signals / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
chemical_list: D010446:Peptide Fragments; D021382:Protein Sorting Signals; D043562:Receptors, G-Protein-Coupled