MuSK is a BMP co-receptor that shapes BMP responses and calcium signaling in muscle cells

Muscle-specific kinase (MuSK) is a receptor tyrosine kinase that is required for the formation and maintenance of neuromuscular junctions. Yilmaz et al . found that MuSK also functions as a co-receptor for bone morphogenetic proteins (BMPs) in myoblasts and in myotubes. MuSK bound to BMPs and BMP receptors in vitro and promoted signaling by BMPs in muscle cells. MuSK promoted the expression of distinct sets of BMP-induced transcripts in myoblasts and myotubes in a manner that was independent of its kinase activity. One of the transcripts stimulated by MuSK-BMP signaling in myoblasts was required for the ability of BMP4 to inhibit intracellular calcium release in response to activation of muscarinic acetylcholine receptors. Thus, in addition to playing a critical role in organizing the neuromuscular junction, MuSK also acts as a BMP co-receptor in developing muscles.