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Efficient synaptic transmission at the neuromuscular junction (NMJ) requires the topological maturation of the postsynaptic apparatus from an oval acetylcholine receptor (AChR)-rich plaque into a complex pretzel-shaped array of branches. However, compared to NMJ formation very little is known about the mechanisms that regulate NMJ maturation. Recently the process of in vivo transformation from plaque into pretzel has been reproduced in vitro by culturing myotubes aneurally on laminin-coated substrate. It was proposed that the formation of complex AChR clusters is regulated by a MuSK-dependent muscle intrinsic program. To elucidate the structure–function role of MuSK in the aneural maturation of AChR pretzels, we used muscle cell lines expressing MuSK mutant and chimeric proteins. Here we report, that besides its role during agrin-induced AChR clustering, MuSK kinase activity is also necessary for substrate-dependent cluster formation. Constitutive-active MuSK induces larger AChR clusters, a faster cluster maturation on laminin and increases the anchorage of AChRs to the cytoskeleton compared to MuSK wild-type. In addition, we find that the juxtamembrane region of MuSK, which has previously been shown to regulate agrin-induced AChR clustering, is unable to induce complex AChR clusters on laminin substrate. Most interestingly, MuSK kinase activity is not sufficient for laminin-dependent AChR cluster formation since the MuSK ectodomain is also required suggesting a so far undiscovered instructive role for the extracellular domain of MuSK.

Parveen, et al.: Studies on Essential Oil of Xanthium strumarium L. LeavesThe hydrodistilled essential oil from Xanthium strumarium L. leaves was analysed by gas chromatographymass spectrometry. Nine out of twenty two constituents were identified from X. strumarium oil. The main components of the oil were β-caryophyllene (17.53%), α-cadinol (6.66%), spathulenol (6.09%), limonene (5.66%) and 1,3,5-trimethyl-2[2-nitroallyl]benzene (3.29%). Phytol (2.42%), α-muurolene (2.08%), copaene (1.47%) were present in appreciable amounts. E,E,Z-1,3,12-nonadecatriene-5,14-diol (0.27%) was present in minor amount. The oil displayed high degree of antifungal effect against all fungal strains with 11.8-46.0 mm zone of inhibition at concentration range 8-250 μg/ml. The 8 μg/ml minimum fungicidal concentration along with being the minimum inhibitory concentration points to the potential of X. strumarium essential oil as a promising source of antifungal agents with useful biomedical applications.

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