Identification and characterization of a novel splice variant of MuSK

MuSK is a receptor tyrosine kinase that initiates the formation of neuromus cular junctions in response to agrin. Little is known about the ligand-indu ced activation and kinase-dependent signalling that leads to the clustering of acetylcholine receptors. The ectodomain of these molecule is composed o f four Ig-like domains. We describe here the isolation of a novel MuSK spli ce variant that lacks the third Ig-like domain in its ectodomain. The corre sponding RNA is the result of alternative splicing which eliminates two exo ns. There is 10 times less mRNA for this shorter form than for the long for m of MuSK and both forms are regulated coordinately. They decrease strongly after birth and are elevated in denervated muscle. Gene transfer by muscle injection of MuSK DNA into individual muscle fibers demonstrates that kina se-induced acetylcholine receptor clustering caused by overexpression of th e two kinases does not depend on the presence of the third Ig-like domain. (C) 1999 Federation of European Biochemical Societies.