title: Identification of Serhl, a new member of the serine hydrolase family induced by passive stretch of skeletal muscle in vivo.
abstract: In response to extended periods of stretch, skeletal muscle typically exhibits cell hypertrophy associated with sustained increases in mRNA and protein synthesis. Several soluble hypertrophic agonists have been identified, yet relatively little is known as to how mechanical load is converted into intracellular signals regulating gene expression or how increased cell size is maintained. In skeletal muscle, hypertrophy is generally regarded as a beneficial adaptive response to increased workload. In some cases, however, hypertrophy can be detrimental as seen in long-term cardiac hypertrophy. Skeletal muscle wasting (atrophy) is a feature of both inherited and acquired muscle disease and normal aging. Elucidating the molecular regulation of cell size is a fundamental step toward comprehending the complex molecular systems underlying muscle hypertrophy and atrophy. Subtractive hybridization between passively stretched and control murine skeletal muscle tissue identified an mRNA that undergoes increased expression in response to passive stretch. Encoded within the mRNA is an open reading frame of 311 amino acids containing a highly conserved type 1 peroxisomal targeting signal and a serine lipase active center. The sequence shows identity to a family of serine hydrolases and thus is named serine hydrolase-like (Serhl). The predicted three-dimensional structure displays a core alpha/beta-hydrolase fold and catalytic triad characteristic of several hydrolytic enzymes. Endogenous Serhl protein immunolocalizes to perinuclear vesicles as does Serhl-FLAG fusion protein transiently expressed in muscle cells in vitro. Overexpression of Serhl-FLAG has no effect on muscle cell phenotype in vitro. Serhl's expression patterns and its response to passive stretch suggest that it may play a role in normal peroxisome function and skeletal muscle growth in response to mechanical stimuli.
authors.affiliation: Molecular Pathology, Vascular Surgery, Division of Surgery and Anaesthetics, Imperial College of Science, Technology and Medicine, Sir Alexander Fleming Building, South Kensington, London, SW7 2AZ, UK.
authors.forename: T J
authors.initials: TJ
authors.lastname: Sadusky
authors.forename: T J
authors.initials: TJ
authors.lastname: Kemp
authors.forename: M
authors.initials: M
authors.lastname: Simon
authors.forename: N
authors.initials: N
authors.lastname: Carey
authors.forename: G R
authors.initials: GR
authors.lastname: Coulton
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018929:Cell Culture Techniques; D003001:Cloning, Molecular; D004247:DNA; D004790:Enzyme Induction; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009119:Muscle Contraction; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism
chemical_list: D009124:Muscle Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D004247:DNA; C431704:Serhl protein, mouse; D012697:Serine Endopeptidases