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 Ca(2+) mobilisation assays revealed nanomolar affinities of HA to GPR37. HA signal transduction through GPR37 was mediated by an inhibitory G protein and required Ca(2+) influx through a channel of the transient receptor potential (TRP) family. It also required activation of Ca(2+)-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.
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http://dx.doi.org/10.1242/jcs.02766 | DOI Listing |
PLoS Biol
January 2025
Department of Biological Sciences, Howard Hughes Medical Institute, Columbia University, New York, New York, United States of America.
Throughout the animal kingdom, several members of the basic helix-loop-helix (bHLH) family act as proneural genes during early steps of nervous system development. Roles of bHLH genes in specifying terminal differentiation of postmitotic neurons have been less extensively studied. We analyze here the function of 5 Caenorhabditis elegans bHLH genes, falling into 3 phylogenetically conserved subfamilies, which are continuously expressed in a very small number of postmitotic neurons in the central nervous system.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Genetics, Silberman Institute of Life Science, Edmond J. Safra Campus, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel.
Secretion of neurotransmitter- and neuropeptide-containing vesicles is a regulated process orchestrated by multiple proteins. Of these, mutants, defective in the and genes, responsible for neurotransmitter and neuropeptide release, respectively, are routinely used to elucidate neural and circuitry functions. While these mutants result in severe functional deficits, their neuroanatomy is assumed to be intact.
View Article and Find Full Text PDFJ Headache Pain
December 2024
Department of Clinical and Molecular Medicine, Sapienza University, Rome, Italy.
Combination treatments for migraine prophylaxis present a promising approach to addressing the diverse and complex mechanisms underlying migraine. This review explores the potential of combining oral conventional prophylactics, onabotulinumtoxin A, monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway, and small molecule CGRP receptor antagonists (gepants). Among the most promising strategies, dual CGRP inhibition through mAbs and gepants may enhance efficacy by targeting both the CGRP peptide and its receptor, while the combination of onabotulinumtoxin A with CGRP treatments offers synergistic pain relief.
View Article and Find Full Text PDFIBRO Neurosci Rep
December 2024
ENT and Head and Neck Research Center and Department, The Five Senses Health Institute, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Expert Opin Pharmacother
December 2024
Department of Urology, General Hospital of Athens "G. Gennimatas", Athens, Greece.
Introduction: Androgen deprivation therapy consists of the cornerstone of prostate cancer medical treatment. Until recently, castration of hypothalamus-hypophysis-gonadal axial was based on injectable medical agents. A few years ago, a novel per os administered GnRH antagonist was approved leading testosterone to castration level.
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