PXD041372 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Multisite phosphorylation by protein kinase A mediates modality-specific modulation of PIEZO2 |
Description | Protein kinase A 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 protein kinase-A 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 domains 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, suggesting that the effect requires multisite phosphorylation. By demonstrating that PIEZO1 is not modulated by PKA, our data also reveals 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. |
HostingRepository | PRIDE |
AnnounceDate | 2023-07-20 |
AnnouncementXML | Submission_2023-07-20_14:06:14.352.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | ThomasMair |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | phosphorylated residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-04-05 23:53:25 | ID requested | |
⏵ 1 | 2023-07-20 14:06:15 | announced | |
Publication List
Schaefer I, Verkest C, Vespermann L, Mair T, Vo, ß H, Zeitzschel N, Lechner SG, PKA mediates modality-specific modulation of the mechanically gated ion channel PIEZO2. J Biol Chem, 299(6):104782(2023) [pubmed] |
Keyword List
submitter keyword: LC-MS/MS, PIEZO2, Protein Kinase A, Proteomics, Phosphorylation |
Contact List
Stefan GLechner |
contact affiliation | Department of Anesthesiology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany. |
contact email | s.lechner@uke.de |
lab head | |
ThomasMair |
contact affiliation | Section for Mass Spectrometry and Proteomics, University Medical Center Hamburg-Eppendorf |
contact email | t.mair@uke.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
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[ - ]
- PRIDE
- PXD041372
- Label: PRIDE project
- Name: Multisite phosphorylation by protein kinase A mediates modality-specific modulation of PIEZO2