AF6/s-afadin is a dual residency protein and localizes to a novel subnuclear compartment.

The AF6/afadin protein is a component of cell membranes at specialized sites of cell-cell contact. Two main splice variants exist, known as l- and s-afadin, respectively. L-afadin is widely expressed in cells of epithelial origin, whilst s-afadin expression is restricted to the brain.

beta-Amyloid induces paired helical filament-like tau filaments in tissue culture.

Paired helical filaments (PHF) are the principal pathologic components of neurofibrillary tangles in Alzheimer's disease (AD). To reproduce the formation of PHF in tissue culture, we stably expressed human tau with and without pathogenic mutations in human SH-SY5Y cells and exposed them for 5 days to aggregated synthetic beta-amyloid peptide (A beta 42). This caused a decreased solubility of tau along with the generation of PHF-like tau-containing filaments.

Molecular properties of fibrin-based matrices for promotion of angiogenesis in vitro.

The molecular properties of fibrin-based matrices, such as fibrillar structure and covalent modifications with adhesion domains, influence the angiogenic behavior of human umbilical vein endothelial cells (HUVECs) in vitro. The fibrillar structure of fibrin-based matrices was influenced by pH but not by covalent incorporation of exogenous adhesion domains. Native fibrin-based matrices polymerized at pH 10 formed organized and longitudinally oriented fibrin fibrils, which provided a good angiogenic substrate for endothelial cells.

Mutagenesis and selection of PDZ domains that bind new protein targets.

PDZ domains are a recently characterized protein-recognition module. In most cases, PDZ domains bind to the C-terminal end of target proteins and are thought thereby to link these target proteins into functional signaling networks. We report the isolation of artificial PDZ domains selected via a mutagenesis screen in vivo, each recognizing a different C-terminal peptide.

The junction-associated protein AF-6 interacts and clusters with specific Eph receptor tyrosine kinases at specialized sites of cell-cell contact in the brain.

The AF-6/afadin protein, which contains a single PDZ domain, forms a peripheral component of cell membranes at specialized sites of cell-cell junctions. To identify potential receptor-binding targets of AF-6 we screened the PDZ domain of AF-6 against a range of COOH-terminal peptides selected from receptors having potential PDZ domain-binding termini. The PDZ domain of AF-6 interacts with a subset of members of the Eph subfamily of RTKs via its COOH terminus both in vitro and in vivo.