PXD054618

PXD054618 is an original dataset announced via ProteomeXchange.

Title	PIEZO1 Interactome in HEK cells
Description	The propeller-shaped blades of the PIEZO1 and PIEZO2 ion channels partition into the plasma membrane and respond to indentation or stretching of the lipid bilayer, thus converting mechanical forces into signals that can be interpreted by cells, in the form of calcium flux and changes in membrane potential. While PIEZO channels participate in diverse physiological processes, from sensing the shear stress of blood flow in the vasculature to detecting a light touch on the surface of the skin, the molecular details that enable these mechanosensors to tune their responses over a vast dynamic range of forces remain largely uncharacterized. To survey the molecular landscape surrounding PIEZO channels at the cell surface, we employed a mass spectrometry-based proteomic approach to capture and identify extracellularly exposed proteins in the vicinity of PIEZO1. This PIEZO1-proximal interactome was enriched in surface proteins localized to cell junctions and signaling hubs within the plasma membrane. Functional screening of these interaction candidates by calcium imaging and electrophysiology in an overexpression system identified the adhesion molecule CADM1/SynCAM that slows the inactivation kinetics of PIEZO1 with little effect on PIEZO2. Conversely, we found that CADM1 knockdown accelerates inactivation of endogenous PIEZO1 in Neuro-2a cells. Systematic deletion of CADM1 domains indicate that the transmembrane region is critical for the observed effects on PIEZO1, suggesting that modulation of inactivation is mediated by interactions in or near the lipid bilayer.
HostingRepository	PRIDE
AnnounceDate	2024-10-30
AnnouncementXML	Submission_2024-10-30_13:08:52.224.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Anna Koster
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-05 23:09:00	ID requested
⏵ 1	2024-10-30 13:08:53	announced

10.1073/pnas.2415934121;

Koster AK, Yarishkin O, Dubin AE, Kefauver JM, Pak RA, Cravatt BF, Patapoutian A, Chemical mapping of the surface interactome of PIEZO1 identifies CADM1 as a modulator of channel inactivation. Proc Natl Acad Sci U S A, 121(41):e2415934121(2024) [pubmed]

submitter keyword: CADM1,PIEZO1, mechanosensation, ion channel

Ben Cravatt
contact affiliation	Scripps Research
contact email	cravatt@scripps.edu
lab head
Anna Koster
contact affiliation	Scripps Research
contact email	akoster@scripps.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/10/PXD054618

PRIDE project URI

• PRIDE
  1. PXD054618
     1. Label: PRIDE project
     2. Name: PIEZO1 Interactome in HEK cells