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PXD042661 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe VE-cadherin/AmotL2 mechanosensory pathway suppresses aortic inflammation and the formation of abdominal aortic aneurysms
DescriptionArterial 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.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Bos taurus (Bovine); NCBI TaxID: 9913;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-06-02 07:26:18ID requested
12023-08-21 03:17:34announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: mechanotransduction,AmotL2, abdominal aortic aneurysms
Contact List
contact affiliationDept. Oncology Pathology, Karolinska Institutet, and Scilifelab, Stockholm, Sweden
contact emailjanne.lehtio@ki.se
lab head
contact affiliationKarolinska Institutet
contact emailgeorgios.mermelekas@scilifelab.se
dataset submitter
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Dataset FTP location
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