title: CAPON expression in skeletal muscle is regulated by position, repair, NOS activity, and dystrophy.
abstract: In skeletal muscle, the localization of nNOS is destabilized in the absence of dystrophin, which impacts muscle function and satellite cell activation. In neurons, the adaptor protein, carboxy-terminal PDZ ligand of nNOS (CAPON), regulates the distribution of neuronal nitric oxide synthase (nNOS), which produces the key signaling molecule nitric oxide (NO). While a CAPON-like gene is known to compensate functionally for a dystrophic phenotype in muscle of Caenorhabditis elegans, CAPON expression has not been reported for mammalian muscle. Here, CAPON expression was identified in mouse muscle using Northern and Western blotting and in situ hybridization in combination with immunostaining for laminin. CAPON RNA was expressed in developing normal and dystrophic muscles near fiber junctions with tendons, and levels increased from 1 to 3 weeks. In regenerating normal muscle and also in dystrophic muscles in the mdx mouse, CAPON transcripts were prominent in satellite cells and new myotubes. Expression of CAPON RNA increased in diaphragm muscle of normal and mdx mice after treatment with L-arginine, the NOS substrate. Both CAPON and utrophin protein levels increased in dystrophic quadriceps muscle after treatment with the steroid deflazacort plus L-arginine, known to reduce the dystrophic phenotype. The identification of CAPON transcripts and protein in mammalian muscle and responses to L-arginine suggest CAPON may have a functional role in stabilizing neuronal NOS in skeletal muscle in the cytoskeletal complex associated with dystrophin/utrophin, with possible applications to therapy for human muscular dystrophy.
authors.affiliation: CNRS-UPR5534, Université Lyon-1 and Institut Cochin, INSERM U567, 75014 Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Ségalat
authors.forename: Karine
authors.initials: K
authors.lastname: Grisoni
authors.forename: Jonathan
authors.initials: J
authors.lastname: Archer
authors.forename: Cinthya
authors.initials: C
authors.lastname: Vargas
authors.forename: Anne
authors.initials: A
authors.lastname: Bertrand
authors.forename: Judy E
authors.initials: JE
authors.lastname: Anderson
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D015153:Blotting, Western; D003964:Diaphragm / Q000378:metabolism; D016189:Dystrophin / Q000172:deficiency; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D017403:In Situ Hybridization; D007797:Laminin / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D009136:Muscular Dystrophies / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011282:Pregnenediones / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D032496:Satellite Cells, Skeletal Muscle / Q000187:drug effects; D013997:Time Factors; D049411:Utrophin / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016189:Dystrophin; D007166:Immunosuppressive Agents; D007797:Laminin; C110667:Nos1ap protein, mouse; D011282:Pregnenediones; D012333:RNA, Messenger; D049411:Utrophin; D001120:Arginine; D019001:Nitric Oxide Synthase; C021988:deflazacort