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activity club 5 problems you can’t blame on how you were raised have a slender figure Note that residual tyrosine kinase activity was detected in some mutant endplates (arrow), which may also result from unrelated tyrosine kinases.Full figure and legend (478K)MUSK is a receptor tyrosine kinase expressed on the muscle cell membrane.5, 11 It consists of an extracellular domain containing IgG like domains, a Frizzled like cysteine rich domain (C6 box), a transmembrane domain and a cytoplasmic domain composed of a juxtamembrane domain and a tyrosine kinase domain (Figure 1c).12, 13 The variant c.1724T p.(Ile575Thr) is located in a highly conserved region at the boundary of the juxtamembrane and kinase domains. The important role of both domains in tyrosine kinase activation and Dok 7 signaling suggests that the variant may affect MUSK signaling and AChR clustering.14, 15 To investigate this, local tyrosine kinase activity and AChR clusters were visualized at nascent motor endplates in muscle biopsies from an affected fetus (case 8, 23 weeks of gestation) and a control fetus aborted at 22 weeks due to cervical insufficiency (Figure 3d Ingrowing axons from motor neurons were visualized with the synaptic vesicle marker Synaptotagmin 1. In wild type tissue, developing motor endplates were closely associated with AChR clusters, stained by In MUSK mutant muscle, these clusters were strongly reduced in number and appeared very small (Figure 3d, e and h).
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