PXD039256

PXD039256 is an original dataset announced via ProteomeXchange.

Title	The VE-cadherin/AmotL2 mechanosensory pathway suppresses aortic inflammation and the formation of abdominal aortic aneurysms
Description	Arterial endothelial cells (ECs) have the ability to respond to mechanical forces exerted by laminar fluid shear stress. This response is of importance, as it is protective against vascular diseases such as atherosclerosis and aortic aneurysms. Mechanical forces are transmitted at the sites of adhesion to the basal membrane as well as cell-cell junctions where protein complexes connect to the cellular cytoskeleton to relay force into the cell. Here we present a novel protein complex that connects junctional VE-cadherin and radial actin filaments to the LINC complex in the nuclear membrane. We show that the scaffold protein AmotL2 is essential for the formation of radial actin filaments and the flow-induced alignment of aortic endothelial cells. The deletion of endothelial AmotL2 alters nuclear shape as well as subcellular positioning. Molecular analysis shows that VE-cadherin is mechanically associated with the nuclear membrane via binding to AmotL2 and Actin. Furthermore, the deletion of AmotL2 in ECs provoked a pro-inflammatory response and abdominal aortic aneurysms (AAA) in the aorta of mice on a normal diet. Remarkably, transcriptome analysis of AAA samples from human patients revealed a negative correlation between AmotL2 expression and inflammation of the aortic intima. These findings provide a conceptual framework regarding how mechanotransduction in the junctions is coupled with vascular diseases.
HostingRepository	PRIDE
AnnounceDate	2024-10-17
AnnouncementXML	Submission_2024-10-17_04:25:25.245.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Georgios Mermelekas
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Bos taurus (Bovine); NCBI TaxID: 9913;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-01-04 04:20:11	ID requested
⏵ 1	2024-10-17 04:25:27	announced

10.1038/s44161-023-00298-8;

Zhang Y, Zhang Y, Hutterer E, Hultin S, Bergman O, Kolbeinsdottir S, Jin H, Forteza MJ, Ketelhuth DFJ, Roy J, Hedin U, Enge M, Matic L, Eriksson P, Holmgren L, The VE-cadherin/AmotL2 mechanosensory pathway suppresses aortic inflammation and the formation of abdominal aortic aneurysms. Nat Cardiovasc Res, 2(7):629-644(2023) [pubmed]

submitter keyword: mechanotransduction,AmotL2, abdominal aortic aneurysms

Janne Lehtiö
contact affiliation	Department of Oncology and Pathology. Karolinska Institutet and Scilifelab, Stockholm, Sweden
contact email	janne.lehtio@ki.se
lab head
Georgios Mermelekas
contact affiliation	Karolinska Institutet
contact email	georgios.mermelekas@scilifelab.se
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/PXD039256

PRIDE project URI

• PRIDE
  1. PXD039256
     1. Label: PRIDE project
     2. Name: The VE-cadherin/AmotL2 mechanosensory pathway suppresses aortic inflammation and the formation of abdominal aortic aneurysms