ATP is stored in lamellar bodies to activate vesicular P2X 4 in an autocrine fashion upon exocytosis.

Autor: Fois G; Institute of General Physiology, Ulm University, Ulm, Germany., Winkelmann VE; Institute of General Physiology, Ulm University, Ulm, Germany., Bareis L; Institute of General Physiology, Ulm University, Ulm, Germany., Staudenmaier L; Institute of General Physiology, Ulm University, Ulm, Germany., Hecht E; Institute of General Physiology, Ulm University, Ulm, Germany., Ziller C; Institute of Analytical and Bioanalytical Chemistry, Ulm University, Ulm, Germany., Ehinger K; Institute of General Physiology, Ulm University, Ulm, Germany., Schymeinsky J; Immunology and Respiratory Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß, Germany., Kranz C; Institute of Analytical and Bioanalytical Chemistry, Ulm University, Ulm, Germany., Frick M; Institute of General Physiology, Ulm University, Ulm, Germany manfred.frick@uni-ulm.de.
Jazyk: angličtina
Zdroj: The Journal of general physiology [J Gen Physiol] 2018 Feb 05; Vol. 150 (2), pp. 277-291. Date of Electronic Publication: 2017 Dec 27.
DOI: 10.1085/jgp.201711870
Abstrakt: Vesicular P2X 4 receptors are known to facilitate secretion and activation of pulmonary surfactant in the alveoli of the lungs. P2X 4 receptors are expressed in the membrane of lamellar bodies (LBs), large secretory lysosomes that store lung surfactant in alveolar type II epithelial cells, and become inserted into the plasma membrane after exocytosis. Subsequent activation of P2X 4 receptors by adenosine triphosphate (ATP) results in local fusion-activated cation entry (FACE), facilitating fusion pore dilation, surfactant secretion, and surfactant activation. Despite the importance of ATP in the alveoli, and hence lung function, the origin of ATP in the alveoli is still elusive. In this study, we demonstrate that ATP is stored within LBs themselves at a concentration of ∼1.9 mM. ATP is loaded into LBs by the vesicular nucleotide transporter but does not activate P2X 4 receptors because of the low intraluminal pH (5.5). However, the rise in intravesicular pH after opening of the exocytic fusion pore results in immediate activation of vesicular P2X 4 by vesicular ATP. Our data suggest a new model in which agonist (ATP) and receptor (P2X 4 ) are located in the same intracellular compartment (LB), protected from premature degradation (ATP) and activation (P2X 4 ), and ideally placed to ensure coordinated and timely receptor activation as soon as fusion occurs to facilitate surfactant secretion.
(© 2018 Fois et al.)
Databáze: MEDLINE
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