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Protein kinase A regulates the degradation rate of Rs acetylcholine receptors
Author(s) -
Xu Rufeng,
Salpeter Miriam M.
Publication year - 1995
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041650105
Subject(s) - protein kinase a , acetylcholine receptor , receptor , microbiology and biotechnology , second messenger system , acetylcholine , intracellular , kinase , reinnervation , degradation (telecommunications) , phosphodiesterase 3 , biology , chemistry , endocrinology , biochemistry , anatomy , telecommunications , computer science
Acetylcholine receptors at the neuromuscular junction of innervated vertebrate muscle (called Rs AChRs) have a stable degradation rate (t 1/2 ∼8–12 days) which accelerates after denervation to a half‐life of ∼3 days, but can be restabilized by reinnervation or by cAMP. We examined the mechanism by which cAMP regulates the Rs degradation rate. When dibutyryl cAMP (DB‐cAMP) was applied to denervated mouse diaphragms in organ culture, it stabilized the accelerated degradation rate of the Rs. We found that this stabilization is reversible upon removal of the DB‐cAMP, is cAMP specific and is mediated by intracellular cAMP. A major observation of this study is that the cAMP‐induced stabilization of Rs AChRs is via protein kinase A (PKA), since H89, a PKA inhibitor, blocked the DB‐cAMP induced stabilization of Rs, and H85, an analog of H89, which does not inhibit PKA but does inhibit other kinases as efficiently as H89, did not prevent the DB‐cAMP‐induced stabilization of Rs degradation. These results suggest that the cAMP messenger system via a PKA‐dependent pathway could be among the mechanisms whereby the nerve regulates AChR degradation. © 1995 Wiley‐Liss Inc.