Extracellular adenosine triphosphate (ATP) activates P2X receptors, which are involved in diverse physiological functions. Using a proteomic approach, we identified the neuronal calcium sensor VILIP1 as interacting with P2X2 receptors. We found that VILIP1 forms a signaling complex in vitro and in vivo with P2X2 receptors and regulates P2X2 receptor sensitivity to ATP, peak response, surface expression, and diffusion. VILIP1 constitutively binds to P2X2 receptors and displays enhanced interactions in an activation- and calcium-dependent manner owing to exposure of its binding segment in P2X2 receptors. VILIP1-P2X2 interactions are also enhanced in hippocampal neurons during conditions of action potential firing known to trigger P2X2 receptor activation. Our data thus reveal a previously unrecognized function for the neuronal calcium sensor protein VILIP1 and a mechanism for regulation of ATP-dependent P2X receptor signaling by neuronal calcium sensors.
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http://dx.doi.org/10.1126/scisignal.1162329 | DOI Listing |
ACS Pharmacol Transl Sci
January 2025
Pharmaceutical Institute, Pharmacology and Toxicology, University of Bonn, Gerhard-Domagk-Str. 3, 53121 Bonn, Germany.
Lipopolysaccharide (LPS)-neutralizing peptides are emerging as new potential therapeutic modalities to treat sepsis and skin infections. Purinergic ligand-gated ion channels (P2X receptors) play a critical role in various biological processes, including inflammation. Recent drug development efforts have significantly focused on the modulation of P2X receptors.
View Article and Find Full Text PDFPharmaceuticals (Basel)
November 2024
Departamento de Ciencias Biomédicas, Facultad de Medicina, Universidad Católica del Norte, Coquimbo 1781421, Chile.
P2X receptor channels are widely expressed in the CNS, where they have multiple functions in health and disease. The rat P2X2a (rP2X2a) receptor channel is modulated by copper, an essential trace element that plays important roles in synaptic modulation and neurodegenerative disorders. Although essential extracellular amino acids that coordinate copper have been identified, the exact mechanism of copper-induced modulation has not been yet elucidated.
View Article and Find Full Text PDFJ Formos Med Assoc
December 2024
Department of Life Science, College of Science, National Taiwan Normal University, 162, Section 1, Heping E. Rd., Taipei, 106, Taiwan. Electronic address:
Background/purpose: The mechanism for long-term hypoxia/ischemia induced bladder underactivity is uncertain. It requires an effectively therapeutic treatment. Therefore, we determined the pathophysiologic mechanisms of long-term bilateral partial iliac arterial occlusion (BPAO)-induced bladder underactivity and explored the therapeutic potential of adipose-derived stem cells (ADSCs) and ADSC-derived microvesicles (MVs) on BPAO-induced bladder dysfunction.
View Article and Find Full Text PDFJ Reprod Dev
December 2024
Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.
Ovulation disorders are a major cause of low pregnancy rates and infertility in humans and livestock. Kisspeptin neurons located in the anteroventral periventricular nucleus (AVPV) are responsible for the generation of the gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) surge and the consequent ovulation in female rodents. The present study aimed to examine whether purinergic neurons are direct upstream stimulators of AVPV kisspeptin neurons that trigger the GnRH/LH surge and consequent ovulation in Kiss1-Cre rats.
View Article and Find Full Text PDFActa Histochem
December 2024
Laboratory of Veterinary Anatomy and Cell Biology, Faculty of Agriculture, Iwate University, Morioka, Japan. Electronic address:
The carotid body is a hypoxia-sensitive chemoreceptor that induces sensory long-term facilitation after exposure to chronic intermittent hypoxia. However, the mechanisms underlying synaptic plasticity in the carotid body remain unknown. In the present study, we examined the immunohistochemical distribution of cannabinoid receptor type 1 (CB1) and type 2 (CB2), which are candidate molecules involved in the modulation of synaptic transmission.
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