title: Postnatal suppression of myomesin, muscle creatine kinase and the M-line in rat extraocular muscle.
abstract: The M-line and its associated creatine kinase (CK) M-isoform (CK-M) are ubiquitous features of skeletal and cardiac muscle. The M-line maintains myosin myofilaments in register, links the contractile apparatus to the cytoskeleton for external force transfer and localizes CK-based energy storage and transfer to the site of highest ATP demand. We establish here that the muscle group responsible for movements of the eye, extraocular muscle (EOM), is divergent from other striated muscles in lacking both an M-line and its associated CK-M. Although an M-line forms during myogenesis, both in vivo and in vitro, it is actively repressed after birth. Transcripts of the major M-line structural proteins, myomesin 1 and myomesin 2, follow the same pattern of postnatal downregulation, while the embryonic heart-specific EH-myomesin 1 transcript is expressed early and retained in adult eye muscle. By immunocytochemistry, myomesin protein is absent from adult EOM sarcomeres. M-line suppression does not occur in organotypic co-culture with oculomotor motoneurons, suggesting that the mechanism for suppression may lie in muscle group-specific activation or workload patterns experienced only in vivo. The M-line is, however, still lost in dark-reared rats, despite the developmental delay this paradigm produces in the visuomotor system and EOMs. EOM was low in all CK isoform transcripts except for the sarcomeric mitochondrial (Ckmt2) isoform. Total CK enzyme activity of EOM was one-third that of hindlimb muscle. These findings are singularly unique among fast-twitch skeletal muscles. Since EOM exhibits isoform diversity for other sarcomeric proteins, the M-line/CK-M divergence probably represents a key physiological adaptation for the unique energetics and functional demands placed on this muscle group in voluntary and reflexive eye movements.
authors.affiliation: Department of Ophthalmology, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH 44106, USA. jdp7@po.cwru.edu
authors.forename: John D
authors.initials: JD
authors.lastname: Porter
authors.forename: Anita P
authors.initials: AP
authors.lastname: Merriam
authors.forename: Bendi
authors.initials: B
authors.lastname: Gong
authors.forename: Sriram
authors.initials: S
authors.lastname: Kasturi
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Zhou
authors.forename: Kurt F
authors.initials: KF
authors.lastname: Hauser
authors.forename: Francisco H
authors.initials: FH
authors.lastname: Andrade
authors.forename: Georgiana
authors.initials: G
authors.lastname: Cheng
mesh_terms: D000222:Adaptation, Physiological; D000595:Amino Acid Sequence; D000818:Animals; D064211:Connectin; D003402:Creatine Kinase / Q000378:metabolism; D052283:Creatine Kinase, MM Form; D017931:DNA Primers; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D009801:Oculomotor Muscles / Q000033:anatomy & histology* / Q000378:metabolism; D017433:Protein Structure, Secondary; D051381:Rats / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012518:Sarcomeres / Q000378:metabolism*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
chemical_list: D064211:Connectin; D017931:DNA Primers; D007527:Isoenzymes; D009124:Muscle Proteins; C577286:Myom1 protein, rat; C577289:Myom2 protein, rat; D003402:Creatine Kinase; D052283:Creatine Kinase, MM Form