Dynamics of muscle caveolae

• Applicant: Professor Dr. Markus Schülke-Gerstenfeld
• Subject Area: Anatomy and Physiology
• Term: from 2007 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 34181657

We demonstrated an almost complete absence of caveolae due to mutations in the PTRF/Cavin gene in patients with a novel type of congenital generalized lipodystrophy (CGL4). In addition to lipodystrophy, the patients also had a striking muscle phenotype. Skeletal muscles were enlarged and showed the “rippling” phenomenon. Furthermore, gross hypertrophy of smooth muscle caused intestinal obstruction and the cardiac muscle was affected with a wide range of various arrhythmias, including long-QT syndrome, sick-sinus syndrome, ventricular, and supraventricular tachycardia. We will now investigate how caveolae are involved in the signaling transduction pathways that guarantee homeostasis and adaption of muscle mass to varying metabolic and mechanical demands. We will rely on novel life-cell-imaging experiments. In addition we will investigate how the signaling cascades are disturbed in primary myoblasts from patients with caveolin-3 and PTRF/Cavin deficiency. As several receptors (e.g. insulin and ActRIIB receptors) co-localize with caveolae, we hypothesize that caveolae might be an ideal vehicle to down- and up-regulate receptor density, simply by internalization under the sarcolemma (endocytosis) and resurfacing (exocytosis). Imaging of these dynamic processes will be accomplished with time-resolved atomic-force microscopy coupled with confocal microscopic localization of EGFP-tagged PTRF and caveolin-3 protein.

• DFG Programme: Clinical Research Units
• Subproject of: KFO 192: Skeletal Muscle Growth Regulation and Dysregulation
• Participating Person: Professorin Dr. Simone Spuler