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Status: Bibliographieeintrag

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Verfasst von:Meyer, Irina [VerfasserIn]   i
 Verkest, Clement [VerfasserIn]   i
 Vespermann, Lucas [VerfasserIn]   i
 Mair, Thomas [VerfasserIn]   i
 Voß, Hannah [VerfasserIn]   i
 Zeitzschel, Nadja [VerfasserIn]   i
 Lechner, Stefan G. [VerfasserIn]   i
Titel:PKA mediates modality-specific modulation of the mechanically gated ion channel PIEZO2
Verf.angabe:Irina Schaefer, Clement Verkest, Lucas Vespermann, Thomas Mair, Hannah Voß, Nadja Zeitzschel, and Stefan G. Lechner
E-Jahr:2023
Jahr:3 June 2023
Umfang:14 S.
Fussnoten:Online verfügbar 4 May 2023, Version des Artikels 3 June 2023 ; Gesehen am 18.09.2023
Titel Quelle:Enthalten in: The journal of biological chemistry
Ort Quelle:Bethesda, Md. : ASBMB Publications, 1905
Jahr Quelle:2023
Band/Heft Quelle:299(2023), 6 vom: Juni, Artikel-ID 104782, Seite 1-14
ISSN Quelle:1083-351X
Abstract:PKA is a downstream effector of many inflammatory mediators that induce pain hypersensitivity by increasing the mechanosensitivity of nociceptive sensory afferent. Here, we examine the molecular mechanism underlying PKA-dependent modulation of the mechanically activated ion channel PIEZO2, which confers mechanosensitivity to many nociceptors. Using phosphorylation site prediction algorithms, we identified multiple putative and highly conserved PKA phosphorylation sites located on intracellular intrinsically disordered regions of PIEZO2. Site-directed mutagenesis and patch-clamp recordings showed that substitution of one or multiple putative PKA sites within a single intracellular domain does not alter PKA-induced PIEZO2 sensitization, whereas mutation of a combination of nine putative sites located on four different intracellular regions completely abolishes PKA-dependent PIEZO2 modulation, though it remains unclear whether all or just some of these nine sites are required. By demonstrating that PIEZO1 is not modulated by PKA, our data also reveal a previously unrecognized functional difference between PIEZO1 and PIEZO2. Moreover, by demonstrating that PKA only modulates PIEZO2 currents evoked by focal mechanical indentation of the cell, but not currents evoked by pressure-induced membrane stretch, we provide evidence suggesting that PIEZO2 is a polymodal mechanosensor that engages different protein domains for detecting different types of mechanical stimuli.
DOI:doi:10.1016/j.jbc.2023.104782
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1016/j.jbc.2023.104782
 Volltext: https://www.sciencedirect.com/science/article/pii/S0021925823018100
 DOI: https://doi.org/10.1016/j.jbc.2023.104782
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:mechanotransduction
 pain
 PIEZO2
 PKA
 post-translational modification
K10plus-PPN:1859813496
Verknüpfungen:→ Zeitschrift

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