The Orai3 channel and AHNAK2 scaffold protein promote the activation of primary human muscle stem cells in vitro
Skeletal muscle is a dynamic tissue able to regenerate in response to injury. This regeneration relies primarily on the activation of precursor cells, known as muscle stem cells (MuSC). Upon activation, skeletal MuSC re-enter the cell cycle and proliferate as myoblasts, which subsequently either differentiate and fuse to form new fibers or return to quiescence to maintain long-term regenerative…
Primary human muscle stem cells rely on activation to regenerate and repair skeletal muscle. This regeneration process involves precursor cells called muscle stem cells that enter the cell cycle and differentiate into new muscle fibers or remain quiescent to maintain regenerative capacity. Researchers generated reserve cells, similar to muscle stem cells, and studied their activation when exposed to a growth medium containing serum.
The study found that Orai3, a calcium channel, plays a unique role in activating reserve cells independently of calcium-dependent mechanisms. Unlike calcium channel activity, Orai3 does not contribute to store-operated calcium entry or calcium response induced by serum stimulation. BioID protein proximity assay revealed that Orai3 interacts with AHNAK2, a large scaffold protein expressed at high levels in myotubes.
Both Orai3 and AHNAK2 are essential for proper myoblast differentiation and reserve cell activation, but they act through distinct signaling pathways. Orai3 directly influences reserve cell fate, while AHNAK2 facilitates reserve cell activation through signals originating from myotubes. These findings offer new insights into the molecular processes governing the activation and quiescence of human muscle stem cells.
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