PloS one, 2014-06, Vol.9 (6), p.e100043-e100043
2014
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- Autor(en) / Beteiligte
- Titel
- Mechanism for adhesion G protein-coupled receptor GPR56-mediated RhoA activation induced by collagen III stimulation
- Ist Teil von
- PloS one, 2014-06, Vol.9 (6), p.e100043-e100043
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2014
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- GPR56 is a member of the adhesion G protein-coupled receptor (GPCR) family. Despite the importance of GPR56 in brain development, where mutations cause a devastating human brain malformation called bilateral frontoparietal polymicrogyria (BFPP), the signaling mechanism(s) remain largely unknown. Like many other adhesion GPCRs, GPR56 is cleaved via a GPCR autoproteolysis-inducing (GAIN) domain into N- and C-terminal fragments (GPR56N and GPR56C); however, the biological significance of this cleavage is elusive. Taking advantage of the recent identification of a GPR56 ligand and the presence of BFPP-associated mutations, we investigated the molecular mechanism of GPR56 signaling. We demonstrate that ligand binding releases GPR56N from the membrane-bound GPR56C and triggers the association of GPR56C with lipid rafts and RhoA activation. Furthermore, one of the BFPP-associated mutations, L640R, does not affect collagen III-induced lipid raft association of GPR56. Instead, it specifically abolishes collagen III-mediated RhoA activation. Together, these findings reveal a novel signaling mechanism that may apply to other members of the adhesion GPCR family.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0100043Titel-ID: cdi_plos_journals_1538588951
- Format
- –
- Schlagworte
- Activation, Adhesion, Amino Acid Sequence, Animals, Binding sites, Biology and Life Sciences, Brain, Brain research, Cancer, Children & youth, Collagen, Collagen (type III), Collagen Type III - pharmacology, Conserved Sequence, Enzyme Activation - drug effects, Evolution, Molecular, G protein-coupled receptors, Gastroenterology, HEK293 Cells, Hospitals, Humans, Immunoglobulins, Ligands, Lipid rafts, Lipids, Malformations of Cortical Development - genetics, Medical schools, Medicine, Membrane Microdomains - drug effects, Membrane Microdomains - metabolism, Mice, Models, Molecular, Molecular Sequence Data, Mutagenesis, Mutation, Polymicrogyria, Protein expression, Protein Structure, Secondary, Protein Transport - drug effects, Proteins, Rafts, Receptors, G-Protein-Coupled - chemistry, Receptors, G-Protein-Coupled - genetics, Receptors, G-Protein-Coupled - metabolism, rhoA GTP-Binding Protein - metabolism, RhoA protein, Signal transduction, Signal Transduction - drug effects, Signaling, Stroke