PXD071371

PXD071371 is an original dataset announced via ProteomeXchange.

Title	Scube2 primes Dispatched and ADAM10-mediated Shh release by recruiting HDL acceptors to the plasma membrane
Description	Sonic hedgehog (Shh) morphogens are lipidated proteins that firmly attach to the outer plasma membrane (PM) of the cells that produce them. The process by which Shh is solubilized includes the transmembrane protein Dispatched1 (Disp), the soluble glycoprotein Scube2, the proteolytic removal of lipidated peptide termini, and the use of soluble lipoproteins (LPPs) as Shh transporters. However, their molecular interplay remains controversial. Here, we demonstrate that A Disintegrin and Metalloproteinase 10, Scube2, and Disp act synergistically to remove Shh from the PM and transfer it to LPP acceptors. We also demonstrate physical Scube2 interactions with LPPs and that these interactions increase Shh release. Finally, we demonstrate that Scube2 strongly binds to heparan sulfate (HS) on cell surfaces. These findings reveal Scube2’s previously unknown role in binding low-abundance, soluble LPP carriers for Shh and recruiting these carriers to HS-rich Shh release sites at the PM to enhance morphogen release.
HostingRepository	PRIDE
AnnounceDate	2026-02-23
AnnouncementXML	Submission_2026-02-22_16:12:21.804.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Janna Puschmann
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-28 09:11:00	ID requested
⏵ 1	2026-02-22 16:12:22	announced

10.1038/s42003-025-09466-x;

Puschmann J, Steffes G, Froese J, Manikowski D, Ehring K, Wittke J, Garbers C, Wegner SV, Grobe K, Scube2 primes Dispatched and ADAM10-mediated Shh release by recruiting HDL acceptors to the plasma membrane. Commun Biol, 9(1):189(2026) [pubmed]

submitter keyword: A Disintegrin and Metalloproteinase 10, cholesterol, Heparan sulfate, Scube2, Dispatched, Hedgehog, high-density lipoprotein

Kay Grobe
contact affiliation	Insitute for Physiologcial Chemistry and Pathobiochemistry University of Muenster Waldeyerstraße 15 48149 Münster Germany
contact email	kgrobe@uni-muenster.de
lab head
Janna Puschmann
contact affiliation	University of Muenster
contact email	janna.puschmann@uni-muenster.de
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/2026/02/PXD071371

PRIDE project URI

• PRIDE
  1. PXD071371
     1. Label: PRIDE project
     2. Name: Scube2 primes Dispatched and ADAM10-mediated Shh release by recruiting HDL acceptors to the plasma membrane