Localization of the calcitonin gene-related peptide receptor complex at the vertebrate neuromuscular junction and its role in regulating acetylcholinesterase expression.
نویسندگان
چکیده
The calcitonin gene-related peptide (CGRP) is released by motor neurons where it exerts both short and long term effects on skeletal muscle fibers. In addition, sensory neurons release CGRP on the surrounding vasculature where it is in part responsible for local vasodilation following muscle contraction. Although CGRP-binding sites have been demonstrated in whole muscle tissue, the type of CGRP receptor and its associated proteins or its cellular localization within the tissue have not been described. Here we show that the CGRP-binding protein referred to as the calcitonin receptor-like receptor is highly concentrated at the avian neuromuscular junction together with its two accessory proteins, receptor activity modifying protein 1 and CGRP-receptor component protein, required for ligand specificity and signal transduction. Using tissue-cultured skeletal muscle we show that CGRP stimulates an increase in intracellular cAMP that in turn initiates down-regulation of acetylcholinesterase expression at the transcriptional level, and, more specifically, inhibits expression of the synaptically localized collagen-tailed form of the enzyme. Together, these studies suggest a specific role for CGRP released by spinal cord motoneurons in modulating synaptic transmission at the neuromuscular junction by locally inhibiting the expression of acetylcholinesterase, the enzyme responsible for terminating acetylcholine neurotransmission.
منابع مشابه
Localization of the CGRP Receptor Complex at the Vertebrate Neuromuscular Junction and its Role in Regulating Acetylcholinesterase Expression
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CGRP, which coexists with acetylcholine in trigeminal motoneurons, could be one of the regulatory anterograde factors responsible for the enhanced expression of AChR subunits in neuromuscular junction. It has been also shown that low level of thyroid hormone plasma concentration has influence on the transitional development of muscle fibers and related motoneurons through a sever reduction in A...
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متن کامل2. Morphological Approach to the Neurotransmission System
At present a number of neuromodulators are found and their localization in the nervous system has been examined by using immunocytochemical technique. One of the most interesting topics in this field is a problem of the colocalization of multiple neuromodulators in single neurons. For example, calcitonin gene-related peptide (CGRP) coexists with acetylcholine (Ach) in single motor neurons inner...
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ورودعنوان ژورنال:
- The Journal of biological chemistry
دوره 278 27 شماره
صفحات -
تاریخ انتشار 2003