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Muscle‐derived neurotrophin‐3 increases the aggregation of acetylcholine receptors in neuron–muscle co‐cultures

Fu, Amy K.Y.1; Ip, Fanny C.F.1; Lai, Kwok O.1; Tsim, Karl W.K.1; Ip, Nancy Y.1,2

Developmental Neuroscience

NEUROTROPHINS, a group of protein ligands that are structurally related to the prototype nerve growth factor (NGF), are prominently expressed in the skeletal muscle during the critical period of synapse formation. In the present study, we utilized a co-culture system of NG108-15 cells expressing the Trk receptors and C2C12 myotubes expressing the individual neurotrophins to examine whether these factors can act in a target-derived manner to influence the postsynaptic specializations. Our findings demonstrated that muscle-derived neurotrophin-3 (NT-3) has the unique ability to enhance the aggregation of acetylcholine receptors (AChRs) on the myotubes following co-culture with NG108-15 cells expressing TrkC. Taken together, our findings suggest that NT-3 can act as a retrograde factor to modulate the postsynaptic specializations.

Department of Biology and Biotechnology Research Institute, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China

2Corresponding Author: Nancy Y. Ip

ACKNOWLEDGEMENTS: We are grateful to Dr George Yancopoulos of Regeneron Pharmaceuticals Inc. for providing the Trk-expressing fibroblast cell lines, and Dr Richard Scheller of Stanford University for the rat agrin cDNAs. This study is supported by Biotechnology Research Institute at The Hong Kong University of Science and Technology and Research Grants Council of Hong Kong (HKUST 529/94M to N.Y.I. and 568/95M to K.W.K.T. and N.Y.I.).

Received 9 September 1997; accepted 5 October 1997

© Lippincott-Raven Publishers.