title: Defective Acetylcholine Receptor Subunit Switch Precedes Atrophy of Slow-Twitch Skeletal Muscle Fibers Lacking ERK1/2 Kinases in Soleus Muscle.
abstract: To test the role of extracellular-signal regulated kinases 1 and 2 (ERK1/2) in slow-twitch, type 1 skeletal muscle fibers, we studied the soleus muscle in mice genetically deficient for myofiber ERK1/2. Young adult mutant soleus was drastically wasted, with highly atrophied type 1 fibers, denervation at most synaptic sites, induction of "fetal" acetylcholine receptor gamma subunit (AChRγ), reduction of "adult" AChRε, and impaired mitochondrial biogenesis and function. In weanlings, fiber morphology and mitochondrial markers were mostly normal, yet AChRγ upregulation and AChRε downregulation were observed. Synaptic sites with fetal AChRs in weanling muscle were ~3% in control and ~40% in mutants, with most of the latter on type 1 fibers. These results suggest that: (1) ERK1/2 are critical for slow-twitch fiber growth; (2) a defective γ/ε-AChR subunit switch, preferentially at synapses on slow fibers, precedes wasting of mutant soleus; (3) denervation is likely to drive this wasting, and (4) the neuromuscular synapse is a primary subcellular target for muscle ERK1/2 function in vivo.
authors.affiliation: Department of Neuroscience and Experimental Therapeutics, Texas A&M University Health Science Center, Bryan, Texas, USA.
authors.forename: Shuo
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Neuroscience and Experimental Therapeutics, Texas A&M University Health Science Center, Bryan, Texas, USA.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Seaberg
authors.affiliation: Department of Neuroscience and Experimental Therapeutics, Texas A&M University Health Science Center, Bryan, Texas, USA.
authors.forename: Ximena
authors.initials: X
authors.lastname: Paez-Colasante
authors.affiliation: Department of Neuroscience and Experimental Therapeutics, Texas A&M University Health Science Center, Bryan, Texas, USA.
authors.forename: Mendell
authors.initials: M
authors.lastname: Rimer
mesh_terms: D000818:Animals; D005260:Female; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018657:Muscle Fibers, Slow-Twitch / Q000201:enzymology / Q000473:pathology*; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology*; D009133:Muscular Atrophy; D018995:Myosin Heavy Chains / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D011978:Receptors, Nicotinic / Q000235:genetics / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; D011978:Receptors, Nicotinic; C559497:acetylcholine receptor gamma, mouse; D018995:Myosin Heavy Chains