induction-experimental-autoimmune-encephalomyelitis-mice-evaluation

Induction of Experimental Autoimmune Encephalomyelitis in Mice and Evaluation of the Disease-dependent Distribution of Immune Cells in Various Tissues

Multiple sclerosis is presumed to be an inflammatory autoimmune disease, which is characterized by lesion formation in the central nervous system (CNS) ...

Fraunhofer IME

Medial collateral ligament (MCL) injuries are the second most common injury resulting in player lost time in elite-level ice hockey.

Incidence and injury characteristics of medial collateral ligament injuries in male collegiate ice hockey players.

After activation by Wnt/β-Catenin ligands, a multi-protein complex assembles at the plasma membrane as membrane-bound receptors and intracellular signal transducers are clustered into the so-called Lrp6-signalosome [Corrected]. However, the mechanism of signalosome formation and dissolution is yet not clear. Our imaging studies of live zebrafish embryos show that the signalosome is a highly dynamic structure. It is continuously assembled by Dvl2-mediated recruitment of the transducer complex to the activated receptors and partially disassembled by endocytosis. We find that, after internalization, the ligand-receptor complex and the transducer complex take separate routes. The Wnt-Fz-Lrp6 complex follows a Rab-positive endocytic path. However, when still bound to the transducer complex, Dvl2 forms intracellular aggregates. We show that this endocytic process is not only essential for ligand-receptor internalization but also for signaling. The μ2-subunit of the endocytic Clathrin adaptor Ap2 interacts with Dvl2 to maintain its stability during endocytosis. Blockage of Ap2μ2 function leads to Dvl2 degradation, inhibiton of signalosome formation at the plasma membrane and, consequently, reduction of signaling. We conclude that Ap2μ2-mediated endocytosis is important to maintain Wnt/β-catenin signaling in vertebrates.

In vivo analysis of formation and endocytosis of the Wnt/β-catenin signaling complex in zebrafish embryos.

Injuries in collegiate ice hockey can result in significant time lost from play. The identification of modifiable risk factors relating to a player's physical fitness allows the development of focused training and injury prevention programs targeted at reducing these risks.

Jennifer Kurz

Project Group for Translational Medicine & Pharmacology

Fraunhofer IME

Induction of Experimental Autoimmune Encephalomyelitis in Mice and Evaluation of the Disease-dependent Distribution of Immune Cells in Various Tissues