P2x4 receptors mediate Ca<sup>2+</sup> release from lysosomes in response to stimulation of P2X7 and H<inf>1</inf> histamine receptors

Tan, Sin-Lih, Barri, Muruj, Atakpa-Adaji, Peace, Taylor, Colin W, Smith, Ewan St. John and Murrell-Lagnado, Ruth D (2021) P2x4 receptors mediate Ca<sup>2+</sup> release from lysosomes in response to stimulation of P2X7 and H<inf>1</inf> histamine receptors. International Journal of Molecular Sciences, 22 (19). a10492 1-15. ISSN 1661-6596

[img] PDF - Published Version
Available under License Creative Commons Attribution.

Download (5MB)

Abstract

The 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.

Item Type: Article
Keywords: Ca2+, P2X4, lysosomes, Animals, Calcium, Calcium Signaling, HeLa Cells, Humans, Intracellular Membranes, Lysosomes, Rats, Receptors, Histamine H1, Receptors, Purinergic P2X4, Receptors, Purinergic P2X7
Schools and Departments: School of Life Sciences > Neuroscience
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 17 Jan 2022 11:12
Last Modified: 17 Jan 2022 11:15
URI: http://sro.sussex.ac.uk/id/eprint/103870

View download statistics for this item

📧 Request an update