Activation of human skeletal muscle stem cells:role of Orai3 ans its partner AHNAK2 in physiological condition and in Duchenne Muscular Dystrophy

Prof. Maud Frieden, University of Geneva


The regeneration process of skeletal muscle is induced after a lesion or an overloaded exercise and
relies on the presence of muscle stem cells, called satellite cells. Our laboratory has been working for
several years with an in vitro model of human muscle regeneration, where activated muscle stem cells
proliferate as myoblasts and differentiate into myotubes, but also reform a quiescent stem cell
population, called reserve cells. Serum stimulation triggered the re-entry into the cell cycle (activation)
of a subset of reserve cells, that is associated with an elevation of the cytosolic calcium concentration.
However, we showed that the activation is independent of the calcium signal while the migration of
reserve cells depends on calcium response. Surprisingly, we identified a calcium channel, Orai3, as
being a key player for reserve cell activation but independently from its calcium channel function.
Furthermore, we found out by a proximity protein assay, that AHNAK2, a large scaffold protein, is a
partner of Orai3. One aim of this project is to determine the role of Orai3 and AHNAK2 in the reserve
cell activation process and the interaction sites between both proteins. The second goal is to determine
the function of both proteins in the context of Duchenne muscular dystrophy. We postulate that these
proteins being overexpressed in the condition of reduced dystrophin expression might be involved in
the pathogenicity of DMD. Overall, this project will bring a better knowledge of the processes of human
muscle stem cell activation and the role of two new players in this process, namely a calcium channel
Orai3 and a scaffold protein AHNAK2. This knowledge will be extended to DMD, a very severe muscular