Structures of C1-IgG1 provide insights into how danger pattern recognition activates complement

Microscopic imaging and technolog

The F-BAR protein pacsin2 inhibits asymmetric VE-cadherin internalization from tensile adherens junctions

Vascular homoeostasis, development and disease critically depend on the regulation of endothelial cell-cell junctions. Here we uncover a new role for the F-BAR protein pacsin2 in the control of VE-cadherin-based endothelial adhesion. Pacsin2 concentrates at focal adherens junctions (FAJs) that are experiencing unbalanced actomyosin-based pulling. FAJs move in response to differences in local cytoskeletal geometry and pacsin2 is recruited consistently to the trailing end of fast-moving FAJs via a mechanism that requires an intact F-BAR domain. Photoconversion, photobleaching, immunofluorescence and super-resolution microscopy reveal polarized dynamics, and organization of junctional proteins between the front of FAJs and their trailing ends. Interestingly, pacsin2 recruitment inhibits internalization of the VE-cadherin complex from FAJ trailing ends and is important for endothelial monolayer integrity. Together, these findings reveal a novel junction protective mechanism during polarized trafficking of VE-cadherin, which supports barrier maintenance within dynamic endothelial tissue

Signaling behind bars: a role for bar domains

In this thesis we describe several novel components of growth factor receptor and RhoGTPase activation and signaling. We have demonstrated that the F-BAR protein PACSIN2 is an important regulator of Rac1 output and, as a consequence, cell spreading and migration. This study further established the importance of traffic in the regulation of RhoGTPase function. In addition, we identified HMHA1 as a novel hematopoietic cell-restricted RhoGAP that regulates the actin cytoskeleton as well as cell spreading. Because expression of the HMHA1 has been observed in epithelial tumor cells as well, future studies should define the mechanisms through which HMHA1 regulates the transformation and invasiveness of these tumor cells. Furthermore, owing to its role as a minor histocompatibility antigen, T cells are generated against epitopes of HMHA1. As the healthy epithelium does not express HMHA1, it might prove an excellent target for tumor therapy. In addition, we describe a novel mechanism through which Rac1 regulates epithelial junction stability independent of the actin cytoskeleton. Although many studies focused on the regulatory role of RhoGTPase in junction remodeling in the context of actin dynamics, our study revealed that additional mechanisms through which RhoGTPases affect cell-cell junctions exist, further underscoring the complexity of RhoGTPase signaling in junction remodeling. Finally, although many pathways that regulate growth factor receptor traffic have already been described, we demonstrate in this thesis a novel component, PACSIN2, that acts as an important regulator of growth factor receptor activation and signaling

Teelt de grond uit bloembollen ; Rapportage onderzoek 2012

Het programma Teelt de Grond uit ontwikkelt rendabele teeltsystemen voor de vollegrondstuinbouw (groenten, bloembollen, boomteelt, fruit en zomerbloemen & vaste planten die voldoen aan de Europese regelgeving voor de waterkwaliteit. Uitgangspunt is dat de systemen naast een sterke emissiebeperking ook voordelen voor ondernemers opleveren ( zoals een grotere arbeids-efficiëntie, betere kwaliteit of nieuwe marktkansen) en gewaardeerd worden door de maatschappij

Teelt de grond uit bloembollen ; Rapportage onderzoek 2012

Het programma Teelt de Grond uit ontwikkelt rendabele teeltsystemen voor de vollegrondstuinbouw (groenten, bloembollen, boomteelt, fruit en zomerbloemen & vaste planten die voldoen aan de Europese regelgeving voor de waterkwaliteit. Uitgangspunt is dat de systemen naast een sterke emissiebeperking ook voordelen voor ondernemers opleveren ( zoals een grotere arbeids-efficiëntie, betere kwaliteit of nieuwe marktkansen) en gewaardeerd worden door de maatschappij