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NG108‐15 cells express neuregulin that induces AChR α‐subunit synthesis in cultured myotubes
Author(s) -
Pun San,
Yang Jie F,
Ng Yu P,
Tsim Karl W.K
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)01369-0
Subject(s) - neuregulin , neuregulin 1 , microbiology and biotechnology , myogenesis , biology , cell culture , erbb , chemistry , receptor , biochemistry , myocyte , genetics
A cholinergic neuroblastoma×glioma hybrid cell line NG108‐15 is able to form functional synapses, and contains both AChR‐aggregating and AChR‐inducing activities when co‐cultured with myotubes. Several lines of evidence indicate that the AChR‐inducing activity of NG108‐15 cells is derived from neuregulin. The conditioned medium of cultured NG108‐15 cells induced the expression of AChR α‐subunit as well as the tyrosine phosphorylation of erbB‐3 receptor. NG108‐15 cells expressed neuregulin with a protein of ∼100 kDa in size and transcripts of ∼6.8 kbp, ∼2.6 kbp and ∼1.8 kbp; mRNAs encoding β1 and α2 isoforms of neuregulin were revealed. NG108‐15 cells were induced to differentiate by chemicals, and the chemical‐induced differentiation of NG108‐15 cells increased the level of neuregulin mRNA expression ∼3‐fold while the expression of a housekeeping gene remained relatively unchanged. The activity of neuregulin in the conditioned medium of NG108‐15 cells was reduced by treating the medium with heparin and anti‐neuregulin antibody. In addition, NG108‐15 cells were transfected with antisense neuregulin cDNA and its expression of neuregulin was reduced, while its neuregulin‐induced tyrosine phosphorylation activity was markedly decreased. This is the first direct demonstration that the NG108‐15 cell‐induced AChR up‐regulation on cultured myotubes is mediated by neuron‐derived neuregulin.