ijms-22-10492-v2.pdf (4.83 MB)
P2x4 receptors mediate Ca2+ release from lysosomes in response to stimulation of P2X7 and H1 histamine receptors
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posted on 2023-06-10, 02:19 authored by Sin-Lih Tan, Muruj BarriMuruj Barri, Peace Atakpa-Adaji, Colin W Taylor, Ewan St. John Smith, Ruth Murrell-LagnadoRuth Murrell-LagnadoThe P2X4 purinergic receptor is targeted to endolysosomes, where it mediates an inward current dependent on luminal ATP and pH. Activation of P2X4 receptors was previously shown to trigger lysosome fusion, but the regulation of P2X4 receptors and their role in lysosomal Ca2+ signaling are poorly understood. We show that lysosomal P2X4 receptors are activated downstream of plasma membrane P2X7 and H1 histamine receptor stimulation. When P2X4 receptors are expressed, the increase in near-lysosome cytosolic [Ca2+] is exaggerated, as detected with a low-affinity targeted Ca2+ sensor. P2X4-dependent changes in lysosome properties were triggered downstream of P2X7 receptor activation, including an enlargement of lysosomes indicative of homotypic fusion and a redistribution of lysosomes towards the periphery of the cell. Lysosomal P2X4 receptors, therefore, have a role in regulating lysosomal Ca2+ release and the regulation of lysosomal membrane trafficking.
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- Published
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- Published version
Journal
International Journal of Molecular SciencesISSN
1661-6596Publisher
MDPIExternal DOI
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19Volume
22Page range
1-15Article number
a10492Event location
SwitzerlandDepartment affiliated with
- Neuroscience Publications
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- Yes
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- Yes
Legacy Posted Date
2022-01-17First Open Access (FOA) Date
2022-01-17First Compliant Deposit (FCD) Date
2022-01-17Usage metrics
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