PXD011490

PXD011490 is an original dataset announced via ProteomeXchange.

Title	Endocytosis by macrophages: Interplay of macrophage scavenger receptor-1 and LDL receptor-related protein-1
Description	Multiple receptors may mediate the cellular uptake of a single protein and thereby affect the plasma level of the involved protein. In case of Von Willebrand Factor (VWF) these receptors include LDL receptor-related protein-1 (LRP-1), Macrophage scavenger receptor-1 (MSR-1, SR-AI or CD204), the Macrophage Galactose-type lectin (CLEC10A, MGL or CD301), Siglec-5 and the Asialoglycoprotein receptor (ASGPR).1 In the present study, we aimed to gain insight into the interplay of multiple receptors to the cellular internalization of a single ligand like VWF. The macrophages in the liver and spleen have been reported to contribute considerably to the cellular uptake of VWF. Previously, we have shown that also human monocyte-derived macrophages (MDMs) internalize VWF via a mechanism that depends on LRP-1.5 We now analyzed the cell surface proteome of MDMs using mass spectrometry analysis to identify putative other VWF clearance receptors on MDMs. We found that MDMs contain LRP-1 and MSR-1, and we identified 1 peptide that is shared by Siglec-5 and Siglec-14. The estimated copy numbers of these receptors revealed a markedly higher expression of LRP-1 and MSR-1 compared to Siglec-5/14. We therefore focused our study on the possible dual mechanism by which LRP-1 and MSR-1 may cooperate in the cellular uptake of VWF by MDMs and conducted a range of functional studies. Based on the data presented in this study, we propose the following model to explain the relationship between the two abundant VWF receptors on MDMs. Both LRP-1 and MSR-1 associate with regions in the D’D3A1 region of VWF, thereby initiating two endocytic pathways that are both regulated by LRP-1. The first pathway follows a direct association of the VWF A1 domain to LRP-1. In the second pathway, VWF interacts to MSR-1 via regions in the D’D3 assembly, which subsequently associates to LRP-1 for endocytosis.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:49:49.618.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eelke Béguin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	biotinylated residue
Instrument	Orbitrap Fusion ETD

Revision	Datetime	Status	ChangeLog Entry
0	2018-10-29 02:49:43	ID requested
1	2019-07-08 01:57:40	announced
⏵ 2	2024-10-22 04:49:50	announced	2024-10-22: Updated project metadata.

10.3324/haematol.2018.210682;

B, é, guin EP, Przeradzka MA, Janssen EFJ, Meems H, Sedek M, van der Zwaan C, Mertens K, van den Biggelaar M, Meijer AB, Mourik MJ, Endocytosis by macrophages: interplay of macrophage scavenger receptor-1 and LDL receptor-related protein-1. Haematologica, 105(3):e133-e137(2020) [pubmed]

curator keyword: Biomedical

submitter keyword: macrophage monocyte VWF U87MG

Alexander Benjamin Meijer
contact affiliation	Department of Molecular and Cellular Hemostasis, Sanquin Research, Amsterdam, the Netherlands; 3Department of Biomolecular Mass Spectrometry and Proteomics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
contact email	s.meijer@sanquin.nl
lab head
Eelke Béguin
contact affiliation	Sanquin Research
contact email	e.beguin@sanquin.nl
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/2019/07/PXD011490

PRIDE project URI

• PRIDE
  1. PXD011490
     1. Label: PRIDE project
     2. Name: Endocytosis by macrophages: Interplay of macrophage scavenger receptor-1 and LDL receptor-related protein-1