The neuropeptide head activator is a high-affinity ligand for the orphan G-protein-coupled receptor GPR37
| Autor: | Atanas Ignatov, Mathias Gelderblom, H. Chica Schaller, Ryosuke Takahashi, Jens Urny, Inga Franke, Meriem Rezgaoui, Yuzuru Imai, Ute Süsens, Günter Glassmeier |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Transfection
Receptors G-Protein-Coupled Phosphatidylinositol 3-Kinases Xenopus laevis Ca2+/calmodulin-dependent protein kinase Chlorocebus aethiops Animals Humans Calcium Signaling Receptor G protein-coupled receptor Cell Death biology Activator (genetics) Neuropeptides Parkinson Disease Cell Biology Molecular biology Pyrrolidonecarboxylic Acid Cytoplasm Mitogen-activated protein kinase COS Cells Calcium-Calmodulin-Dependent Protein Kinases Oocytes biology.protein Calcium Mitogens Signal transduction |
| Zdroj: | Journal of Cell Science. 119:542-549 |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.02766 |
| Popis: | The neuropeptide head activator (HA) is a mitogen for mammalian cell lines of neuronal or neuroendocrine origin. HA signalling is mediated by a G-protein-coupled receptor (GPCR). Orphan GPCRs with homology to peptide receptors were screened for HA interaction. Electrophysiological recordings in frog oocytes and in mammalian cell lines as well as Ca2+ mobilisation assays revealed nanomolar affinities of HA to GPR37. HA signal transduction through GPR37 was mediated by an inhibitory G protein and required Ca2+ influx through a channel of the transient receptor potential (TRP) family. It also required activation of Ca2+-dependent calmodulin kinase and phosphoinositide 3-kinase. Respective inhibitors blocked HA signalling and HA-induced mitosis in GPR37-expressing cells. HA treatment resulted in internalisation of GPR37. Overexpression of GPR37 led to aggregate formation, retention of the receptor in the cytoplasm and low survival rates of transfected cells, confirming the notion that misfolded GPR37 contributes to cell death, as observed in Parkinson's disease. |
| Databáze: | OpenAIRE |
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