Published 1 April 2002. doi:10.1083/jcb1571iti2
© The Rockefeller University Press,
0021-9525/2002/4/10-a $5.00
The Journal of Cell Biology, Volume 157, Number 1, April 1, 2002 10-a-10
Clash of the titin
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Sarcomere thick filaments (white) are disrupted by inhibition of titin–MURF-1 binding (right).
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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.
MURF-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.
Now 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.
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. 
Nicole LeBrasseur
lebrasn{at}rockefeller.edu
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