Wnt/β-Catenin Signaling Induces Integrin α4β1 in T Cells and Promotes a Progressive Neuroinflammatory Disease in Mice.

The mechanisms leading to autoimmune and inflammatory diseases in the CNS have not been elucidated. The environmental triggers of the aberrant presence of CD4 T cells in the CNS are not known. In this article, we report that abnormal β-catenin expression in T cells drives a fatal neuroinflammatory disease in mice that is characterized by CNS infiltration of T cells, glial activation, and progressive loss of motor function.

Neuromuscular synapse integrity requires linkage of acetylcholine receptors to postsynaptic intermediate filament networks via rapsyn-plectin 1f complexes.

Mutations in the cytolinker protein plectin lead to grossly distorted morphology of neuromuscular junctions (NMJs) in patients suffering from epidermolysis bullosa simplex (EBS)-muscular dystrophy (MS) with myasthenic syndrome (MyS). Here we investigated whether plectin contributes to the structural integrity of NMJs by linking them to the postsynaptic intermediate filament (IF) network. Live imaging of acetylcholine receptors (AChRs) in cultured myotubes differentiated ex vivo from immortalized plectin-deficient myoblasts revealed them to be highly mobile and unable to coalesce into stable clusters, in contrast to wild-type cells.

Signs of cardiac autonomic imbalance and proarrhythmic remodeling in FTO deficient mice.

In humans, variants of the fat mass and obesity associated (FTO) gene have recently been associated with obesity. However, the physiological function of FTO is not well defined. Previous investigations in mice have linked FTO deficiency to growth retardation, loss of white adipose tissue, increased energy metabolism and enhanced systemic sympathetic activation.

Enhanced fear expression in Spir-1 actin organizer mutant mice.

Spir proteins nucleate actin filaments at vesicle membranes and facilitate intracellular transport processes. The mammalian genome encodes two Spir proteins, namely Spir-1 and Spir-2. While the mouse spir-2 gene has a rather broad expression pattern, high levels of spir-1 expression are restricted to the nervous system, oocytes, and testis.

Systematic identification of proteins that elicit drug side effects.

Side effect similarities of drugs have recently been employed to predict new drug targets, and networks of side effects and targets have been used to better understand the mechanism of action of drugs. Here, we report a large-scale analysis to systematically predict and characterize proteins that cause drug side effects. We integrated phenotypic data obtained during clinical trials with known drug-target relations to identify overrepresented protein-side effect combinations.