PXD022291-1

PXD022291 is an original dataset announced via ProteomeXchange.

Title	Decoding functional high-density lipoprotein particle surfaceome interactions
Description	High-density lipoprotein (HDL) is a mixture of complex particles mediating reverse cholesterol transport (RCT) and several cytoprotective activities. Despite its relevance for human health, many aspects of HDL-mediated lipid trafficking and cellular signaling remain elusive at the mo-lecular level. During HDL’s journey throughout the body, its functions are mediated through in-teractions with cell surface receptors on different cell types. To characterize and better under-stand the functional interplay between HDL particles and tissue, we analyzed the sur-faceome-residing receptor neighborhoods with which HDL potentially interacts. We applied a combination of chemoproteomic technologies including automated cell surface capturing (au-to-CSC) and HATRIC-based ligand–receptor capturing (HATRIC-LRC) on four different cellular model systems mimicking tissues relevant for RCT. The surfaceome analysis of EA.hy926, HEPG2, foam cells, and human aortic endothelial cells (HAECs) revealed the main currently known HDL scavenger receptor B1 (SCRB1), as well as 155 shared cell surface receptors repre-senting potential HDL-receptor interaction candidates . Since vascular endotheli-al growth factor A (VEGF-A) was recently found as a regulatory factor of transendothelial transport of HDL, we next analyzed the VEGF-modulated surfaceome of HAEC using the au-to-CSC technology. VEGF-A treatment led to the remodeling of the surfaceome of HAEC cells, including the previously reported higher surfaceome abundance of SCRB1. In total, 165 addition-al receptors were found on HAEC upon VEGF-A treatment representing SCRB1 co-regulated re-ceptors potentially involved in HDL function. Using the HATRIC-LRC technology on human endothelial cells, we specifically aimed for the identification of other bona fide (co-)receptors of HDL beyond SCRB1. HATRIC-LRC enabled, next to SCRB1, the identification of the receptor ty-rosine-protein kinase Mer (MERTK). Through RNA interference, we revealed its contribution to endothelial HDL binding and uptake. Furthermore, subsequent proximity ligation assays (PLAs) demonstrated the spatial vicinity of MERTK and SCRB1 on the endothelial cell surface. The data shown provide direct evidence for a complex and dynamic HDL receptome and that receptor nanoscale organization may influence binding and uptake of HDL.
HostingRepository	MassIVE
AnnounceDate	2022-08-19
AnnouncementXML	Submission_2022-08-19_06:30:51.749.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sandra Goetze
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	Carbamidomethyl; Oxidation; Deamidated
Instrument	Orbitrap Fusion ETD

Revision	Datetime	Status	ChangeLog Entry
0	2020-11-02 02:24:42	ID requested
⏵ 1	2022-08-19 06:30:52	announced

no publication

submitter keyword: proteomics, HDL, cell surface capture, CSC, ligand receptor capture, LRC, HATRIC, nanoscale organization

Bernd Wollscheid
contact affiliation	ETHZ
contact email	bernd.wollscheid@hest.ethz.ch
lab head
Sandra Goetze
contact affiliation	ETHZ
contact email	sgoetze@ethz.ch
dataset submitter

MassIVE dataset URI

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