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The sarcomere is more than a complicated piece of structural machinery. According to new results by McElhinny et al. (page 125), a building block of striated muscle cells called MURF-1 may also indirectly regulate gene expression.( _# W: x, D& ?" ^6 I" d: {
3 j' J- Y5 h: tMURF-1 localizes to sarcomeres thanks to its interaction with titin, a major structural component of the muscle sarcomere, and the largest vertebrate protein identified to date. Titin is anchored at the sarcomere Z-lines, as are thin (actin) filaments. From there it stretches across entire half sarcomeres to overlap at the mid-line (M-line), where it helps anchor thick (myosin) filaments in a central location.
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' l5 c' Z6 x1 BNow McElhinny et al. show that different domains of titin perform independent functions. Disturbance of the titin–MURF-1 interaction leads to a complete disruption of M-line and thick filament structure. But the remaining titin regions can still stabilize sarcomeric thin filaments and Z-lines.
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Then there is the nuclear connection. The authors demonstrate nuclear localization of MURF-1, and interaction with a glucocorticoid-responsive transcriptional activator. Thus, titin may recognize structural alterations in the sarcomere and signal to the nucleus by releasing MURF-1 for translocation to the nucleus and transcriptional activation. A possible mechanism could involve titin phosphorylation of MURF-1, as titin's kinase domain lies adjacent to its MURF-1–binding domain.(Sarcomere thick filaments (white) are di) |
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发表于 2009-3-6 00:04
发表于 2015-5-27 14:10
