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      Sperm ion channels and transporters in male fertility and infertility

      , ,
      Nature Reviews Urology
      Springer Science and Business Media LLC

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          Calcium signaling.

          Calcium ions (Ca(2+)) impact nearly every aspect of cellular life. This review examines the principles of Ca(2+) signaling, from changes in protein conformations driven by Ca(2+) to the mechanisms that control Ca(2+) levels in the cytoplasm and organelles. Also discussed is the highly localized nature of Ca(2+)-mediated signal transduction and its specific roles in excitability, exocytosis, motility, apoptosis, and transcription.
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            Trends in GPCR drug discovery: new agents, targets and indications

            G protein-coupled receptors (GPCRs) are the most intensively studied drug targets, largely due to their substantial involvement in human pathophysiology and their pharmacological tractability. Here, we report the first analysis of all GPCR drugs and agents in clinical trials. This reveals the current trends across molecule types, drug targets and therapeutic indications, including showing that 481 drugs (~34% of all drugs approved by the FDA) act at 107 unique GPCR targets. Approximately 320 agents are currently in clinical trials, of which ~36% target 64 potentially novel GPCR targets without an approved drug, and the number of biological drugs, allosteric modulators and biased agonists has grown. The major disease indications for GPCR modulators show a shift towards diabetes, obesity, and Alzheimer’s disease, while other central nervous system disorders remain highly represented. The 227 (57%) non-olfactory GPCRs that are yet to be explored in clinical trials have broad untapped therapeutic potential, particularly in genetic and immune system disorders. Finally, we provide an interactive online resource to analyse and infer trends in GPCR drug discovery.
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              Intracellular Ca2+Sensing: Its Role in Calcium Homeostasis and Signaling.

              Ca2+is a ubiquitous intracellular messenger that controls diverse cellular functions but can become toxic and cause cell death. Selective control of specific targets depends on spatiotemporal patterning of the calcium signal and decoding it by multiple, tunable, and often strategically positioned Ca2+-sensing elements. Ca2+is detected by specialized motifs on proteins that have been biochemically characterized decades ago. However, the field of Ca2+sensing has been reenergized by recent progress in fluorescent technology, genetics, and cryo-EM. These approaches exposed local Ca2+-sensing mechanisms inside organelles and at the organellar interfaces, revealed how Ca2+binding might work to open some channels, and identified human mutations and disorders linked to a variety of Ca2+-sensing proteins. Here we attempt to place these new developments in the context of intracellular calcium homeostasis and signaling.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                Nature Reviews Urology
                Nat Rev Urol
                Springer Science and Business Media LLC
                1759-4812
                1759-4820
                January 2021
                November 19 2020
                January 2021
                : 18
                : 1
                : 46-66
                Article
                10.1038/s41585-020-00390-9
                33214707
                cde236b0-48b6-45c4-870c-a990de4b51b8
                © 2021

                http://www.springer.com/tdm

                http://www.springer.com/tdm

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