title: Paradoxical absence of M lines and downregulation of creatine kinase in mouse extraocular muscle.
abstract: The M lines are structural landmarks in striated muscles, necessary for sarcomeric stability and as anchoring sites for the M isoform of creatine kinase (CK-M). These structures, especially prominent in fast skeletal muscles, are missing in rodent extraocular muscle, a particularly fast and active muscle group. In this study, we tested the hypotheses that 1). myomesin and M protein (cytoskeletal components of the M lines) and CK-M are downregulated in mouse extraocular muscle compared with the leg muscles, gastrocnemius and soleus; and 2). the expression of other cytosolic and mitochondrial CK isoforms is correspondingly increased. As expected, mouse extraocular muscles expressed lower levels of myomesin, M protein, and CK-M mRNA than the leg muscles. Immunocytochemically, myomesin and M protein were not detected in the banding pattern typically seen in other skeletal muscles. Surprisingly, message abundance for the other known CK isoforms was also lower in the extraocular muscles. Moreover, total CK activity was significantly decreased compared with that in the leg muscles. Based on these data, we reject our second hypothesis and propose that other energy-buffering systems may be more important in the extraocular muscles. The downregulation of major structural and metabolic elements and relative overexpression of two adenylate kinase isoforms suggest that the extraocular muscle group copes with its functional requirements by using strategies not seen in typical skeletal muscles.
authors.affiliation: Department of Neurology, Case Western Reserve University, Cleveland, OH 44106-5040, USA. fha@po.cwru.edu
authors.forename: Francisco H
authors.initials: FH
authors.lastname: Andrade
authors.forename: Anita P
authors.initials: AP
authors.lastname: Merriam
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Georgiana
authors.initials: G
authors.lastname: Cheng
authors.forename: Colleen A
authors.initials: CA
authors.lastname: McMullen
authors.forename: Katrin
authors.initials: K
authors.lastname: Hayess
authors.forename: Peter F M
authors.initials: PF
authors.lastname: van der ven
authors.forename: John D
authors.initials: JD
authors.lastname: Porter
mesh_terms: D000263:Adenylate Kinase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D064211:Connectin; D003402:Creatine Kinase / Q000378:metabolism*; D052283:Creatine Kinase, MM Form; D015536:Down-Regulation; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009801:Oculomotor Muscles / Q000033:anatomy & histology* / Q000201:enzymology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D064211:Connectin; D006023:Glycoproteins; D007527:Isoenzymes; D009124:Muscle Proteins; D012333:RNA, Messenger; C023587:protein M (glycoprotein); D003402:Creatine Kinase; D052283:Creatine Kinase, MM Form; D000263:Adenylate Kinase