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2014 ◽  
Vol 204 (2) ◽  
pp. 187-202 ◽  
Author(s):  
Sebastian Kötter ◽  
Andreas Unger ◽  
Nazha Hamdani ◽  
Patrick Lang ◽  
Matthias Vorgerd ◽  
...  

In myocytes, small heat shock proteins (sHSPs) are preferentially translocated under stress to the sarcomeres. The functional implications of this translocation are poorly understood. We show here that HSP27 and αB-crystallin associated with immunoglobulin-like (Ig) domain-containing regions, but not the disordered PEVK domain (titin region rich in proline, glutamate, valine, and lysine), of the titin springs. In sarcomeres, sHSP binding to titin was actin filament independent and promoted by factors that increased titin Ig unfolding, including sarcomere stretch and the expression of stiff titin isoforms. Titin spring elements behaved predominantly as monomers in vitro. However, unfolded Ig segments aggregated, preferentially under acidic conditions, and αB-crystallin prevented this aggregation. Disordered regions did not aggregate. Promoting titin Ig unfolding in cardiomyocytes caused elevated stiffness under acidic stress, but HSP27 or αB-crystallin suppressed this stiffening. In diseased human muscle and heart, both sHSPs associated with the titin springs, in contrast to the cytosolic/Z-disk localization seen in healthy muscle/heart. We conclude that aggregation of unfolded titin Ig domains stiffens myocytes and that sHSPs translocate to these domains to prevent this aggregation.



2011 ◽  
Vol 20 (3) ◽  
pp. 347-356 ◽  
Author(s):  
A. Ayme-Southgate ◽  
R. A. Philipp ◽  
R. J. Southgate


2010 ◽  
Vol 98 (3) ◽  
pp. 553a
Author(s):  
Brian Anderson ◽  
Julius Bogolomovas ◽  
Siegfried Labeit ◽  
Henk Granzier


2008 ◽  
Vol 67 (6) ◽  
pp. 653-669 ◽  
Author(s):  
Agnes J. Ayme-Southgate ◽  
Richard J. Southgate ◽  
Richard A. Philipp ◽  
Erik E. Sotka ◽  
Catherine Kramp




2007 ◽  
Vol 93 (6) ◽  
pp. 2102-2109 ◽  
Author(s):  
Pasquale Bianco ◽  
Attila Nagy ◽  
András Kengyel ◽  
Dávid Szatmári ◽  
Zsolt Mártonfalvi ◽  
...  


2006 ◽  
Vol 26 (6-8) ◽  
pp. 467-477 ◽  
Author(s):  
Agnes Ayme-Southgate ◽  
Judith Saide ◽  
Richard Southgate ◽  
Christophe Bounaix ◽  
Anthony Cammarato ◽  
...  
Keyword(s):  


2005 ◽  
Vol 89 (1) ◽  
pp. 329-336 ◽  
Author(s):  
A. Nagy ◽  
L. Grama ◽  
T. Huber ◽  
P. Bianco ◽  
K. Trombitás ◽  
...  
Keyword(s):  


2004 ◽  
Vol 117 (24) ◽  
pp. 5781-5789 ◽  
Author(s):  
A. Nagy


2003 ◽  
Vol 998 (1) ◽  
pp. 351-355
Author(s):  
MIRTA MIHOVILOVIC ◽  
EMMA CIAFALONI ◽  
JENNIFER BUTTERWORTH-ROBINETTE ◽  
JIAN-PING JIN ◽  
JANICE MASSEY ◽  
...  


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