Abstract
Mechanical factors such as stretch are thought to be important in the regulation of muscle phenotype. Small muscle protein X-linked (SMPX) is upregulated by stretch in skeletal muscle and has been suggested to serve both as a transcription factor and a mechanosensor, possibly giving rise to changes in both fiber size and fiber type. We have used in vivo confocal imaging to study the subcellular localization of SMPX in skeletal muscle fibers of adult rats using a SMPX-EGFP fusion protein. The fusion protein was localized predominantly in repetitive double stripes flanking the Z-disc, and was excluded from all nuclei. This localization would be consistent with SMPX being a mechanoreceptor, but not with SMPX playing a role as a transcription factor. In vivo overexpression of ectopic SMPX in skeletal muscle of adult mice gave no significant changes in fiber type distribution or cross sectional area, thus a role of SMPX in regulating muscle phenotype remains unclear.
Highlights
Skeletal muscle displays a remarkable ability to adapt to variable conditions such as electrical activity, hormones and mechanical load
Small Muscle Protein X-linked (SMPX) is localized to the costameres, both in vivo and in C2C12 cells [14], and it coprecipitates with vinculin, a major constituent of the costameres [10,13]
It has previously been postulated that SMPX may serve as a transcription factor
Summary
Skeletal muscle displays a remarkable ability to adapt to variable conditions such as electrical activity, hormones and mechanical load. The most likely candidate structure for mechanotransduction in muscle cells are the costameres, demonstrated to be important for lateral force transmission during muscle contraction [9]. These are cytoskeletal protein complexes arranged so that they flank the Z-line and overlie the I-band of sarcomeres and anchor the sarcomeres to the extracellular matrix [10]. One of the candidate proteins for mechanotransduction is Small Muscle Protein X-linked (SMPX), a 9 kD protein predominantly expressed in cardiac and skeletal muscle. SMPX is localized to the costameres, both in vivo and in C2C12 cells [14], and it coprecipitates with vinculin, a major constituent of the costameres [10,13]
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