The Calcitonin Gene-Related Peptide-Induced Acetylcholinesterase Synthesis in Cultured Chick Myotubes Is Mediated by Cyclic AMP |
| |
Authors: | Roy C. Y. Choi Lisa Y. Yung Tina T. X. Dong David C. C. Wan Yung H. Wong Karl W. K. Tsim |
| |
Affiliation: | Department of Biology and Biotechnology Research Institute, Hong Kong University of Science and Technology, and; Department of Biochemistry, Chinese University of Hong Kong, China |
| |
Abstract: | Abstract: In vertebrate neuromuscular junctions, post-synaptic specialization includes aggregation of acetylcholine receptors (AChRs) and acetylcholinesterase (AChE). The motor nerve provides soluble factors and electrical activity to achieve this striking localization of AChRs/AChE. Calcitonin gene-related peptide (CGRP), a neuropeptide synthesized by motor neurons, is able to stimulate the expression of AChR in cultured myotubes. Similar to AChR regulation, synthesis of AChE in cultured chick myotubes is also stimulated by CGRP. Application of CGRP onto cultured myotubes stimulated the accumulation of intracellular cyclic AMP (cAMP) as well as the expression of AChE mRNA and protein. However, the enzymatic activity of AChE remained unchanged. In cultured myotubes, various drugs affecting the intracellular level of cAMP, such as N 6, O 2'-dibutyryladenosine 3',5'-cyclic monophosphate, cholera toxin, and forskolin, could mimic the effect of CGRP in stimulating the expression of AChE. When myotubes were transfected with cDNA encoding constitutively active mutant Gαs, the intracellular cAMP synthesis was increased. The increase in cAMP level was in parallel with an increase in the expression of AChE, whereas transfection of active mutant Gαi cDNA decreased the cAMP level as well as the AChE expression. In addition, expression of collagen-tailed AChE was up-regulated by the cAMP pathway. These findings indicated that CGRP-induced AChE regulation is mediated by the cAMP pathway and represented the first evidence to suggest that the regulation of mRNA synthesis of AChR and AChE can be mediated by the same neuron-derived factor. |
| |
Keywords: | Acetylcholine receptor Neuromuscular junction Neurotrophic factors Synapse formation |
|
|