We evaluated the role of IP(3) in sugar taste reception in Drosophila melanogaster by inactivating the IP(3) signaling using genetic tools. We used the "IP(3) sponge," composed of the modified ligand-binding domain from the mouse IP(3) receptor, which was designed to absorb IP(3) in competition with native IP(3) receptors. Another tool was a transgene that generates double-stranded RNA against IP(3) receptor mRNA. Both inhibitors diminished the sensitivity of flies to trehalose and sucrose, as estimated by behavioral assays and electrophysiological recordings from the sugar receptor cells. The result indicates that IP(3) signaling is indispensable for sugar reception in Drosophila.
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http://dx.doi.org/10.1080/01677060600569713 | DOI Listing |
Contact (Thousand Oaks)
December 2024
Department of Physiology and Membrane Biology, University of California, Davis, CA, USA.
Membrane contact sites (MCSs) are specialized regions where two or more organelle membranes come into close apposition, typically separated by only 10-30 nm, while remaining distinct and unfused. These sites play crucial roles in cellular homeostasis, signaling, and metabolism. This review focuses on ion channels, transporters, and receptors localized to MCSs, with particular emphasis on those associated with the plasma membrane and endoplasmic reticulum (ER).
View Article and Find Full Text PDFBiomed Khim
December 2024
Center for Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, Moscow, Russia; Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
Anuclear blood cells, platelets, are the basis for the formation of blood clots in human vessels. While antiplatelet therapy is most often used after ischemic events, there is a need for its personalization due to the limited effectiveness and risks of bleeding. Previously, we developed a series of computational models to describe intracellular platelet signaling and a set of experimental methods to characterize the platelets of a given patient.
View Article and Find Full Text PDFFront Cell Dev Biol
December 2024
MitoCare Center, Department of Pathology and Genomic Medicine, Thomas Jefferson University, Philadelphia, PA, United States.
The activation of IP receptor (IPR) Ca channels generates agonist-mediated Ca signals that are critical for the regulation of a wide range of biological processes. It is therefore surprising that CRISPR induced loss of all three IPR isoforms (TKO) in HEK293 and HeLa cell lines yields cells that can survive, grow and divide, albeit more slowly than wild-type cells. In an effort to understand the adaptive mechanisms involved, we have examined the activity of key Ca dependent transcription factors (NFAT, CREB and AP-1) and signaling pathways using luciferase-reporter assays, phosphoprotein immunoblots and whole genome transcriptomic studies.
View Article and Find Full Text PDFJ Biol Chem
December 2024
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, 37232; Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, 37232. Electronic address:
Mechanistic Target of Rapamycin (mTOR) binds the small metabolite inositol hexakisphosphate (IP) as shown in structures of mTOR, however it remains unclear if IP, or any other inositol phosphate species, function as an integral structural element(s) or catalytic regulator(s) of mTOR. Here, we show that multiple, exogenously added inositol phosphate species can enhance the ability of mTOR and mTORC1 to phosphorylate itself and peptide substrates in in vitro kinase reactions, with the higher order phosphorylated species being more potent (IP=IP>IP>>IP). IP increased the V and decreased the apparent K of mTOR for ATP.
View Article and Find Full Text PDFPLoS Comput Biol
December 2024
Department of Physics, School of Philosophy, Sciences and Letters of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Astrocytes respond to neurotransmitters by increasing their intracellular Ca2+ concentration (Ca2+ signals). While glutamate released by neurons trigger Ca2+ signals through IP3- and glutamate transporter-dependent mechanisms, dopamine released in distant sites activates astrocytes via dopaminergic receptors. However, little is known about the modulatory effects of dopamine on glutamate-evoked astrocytic activity.
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