Identification of Serhl, a new member of the serine hydrolase family induced by passive stretch of skeletal muscle in vivo

In response to extended periods of stretch, skeletal muscle typically exhib its cell hypertrophy associated with sustained increases in mRNA and protei n synthesis, Several soluble hypertrophic agonists have been identified, ye t relatively little is known as to how mechanical load is converted into in tracellular signals regulating gene expression or how increased cell size i s maintained. In skeletal muscle, hypertrophy is generally regarded as a be neficial adaptive response to increased workload. In some cases, however, h ypertrophy can be detrimental as seen in long-term cardiac hypertrophy, Ske letal muscle wasting (atrophy) is a feature of both inherited and acquired muscle disease and normal aging. Elucidating the molecular regulation of ce ll size is a fundamental step toward comprehending the complex molecular sy stems underlying muscle hypertrophy and atrophy. Subtractive hybridization between passively stretched and control murine skeletal muscle tissue ident ified an mRNA that undergoes increased expression in response to passive st retch. Encoded within the mRNA is an open reading frame of 311 amino acids containing a highly conserved type I peroxisomal targeting signal and a ser ine 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 Se rhl protein immunolocalizes to perinuclear vesicles as does Serhl-FLAG: fus ion protein transiently expressed in muscle cells in vitro. Overexpression of Serhl-FLAG has no effect on muscle cell phenotype in vitro. Serhl's expr ession patterns and its response to passive stretch suggest that it may pla y a role in normal peroxisome function and skeletal muscle growth in respon se to mechanical stimuli. (C) 2001 Academic Press.