Project B01

VE-Cadherin Modifications and Binding Partners Regulate Endothelial Junctions

The induction of vascular permeability and the entry of leukocytes into tissue are hallmarks of inflammation. Both processes are controlled by mechanisms that regulate the integrity of endothelial junctions, a very dynamic cellular interphase. VE-cadherin is a central adhesion molecule that provides stability of endothelial junctions and controls junction integrity. Anchoring of VE-cadherin to the actin cytoskeleton is essential for its adhesive function. This link to actin is mediated by catenins, which represent key players for the regulation of endothelial junctions by largely unknown mechanisms. Analyzing mice with mutations in VE-cadherin, we established its role as determinant for vessel integrity in various organs and vascular beds. Point mutations in certain tyrosine residues within the cytoplasmic domain of VE-cadherin revealed that in vivo phosphorylation of such sites represents an important regulatory step that control induction of permeability and leukocyte extravasation. In this proposal, we will investigate the molecular mechanisms whereby tyrosine residues control the adhesive function of VE-cadherin in vivo. In addition, we will analyze the relevance of the interaction of VE-cadherin with VEGFR2, plakoglobin and vinculin (via a-catenin) for the regulation of endothelial junctions in vivo.

Rafael being pulled to the Badestrasse after the graduation ceremony

Rafael Krämer - first graduated PhD Student from the CRC1348 IRTG

We are happy to announce that in December 2019 Rafael Krämer from the Rumpf lab was graduated as first PhD student from the CRC1348 IRTG. Congratulations Dr. Krämer and well done!

CRC1348 Retreat 2019 Oberwerries

CRC 1348 Retreat 2019 Oberwerries

The CRC has staged a successful and productive annual retreat at the Landesturnschule Oberwerries with lots of mental and some physical exercise. We are due to return fully equipped with sweat pants, trainers and shower gel in 2020!