Author/Authors :
Ralph Kn?ll، نويسنده , , Masahiko Hoshijima، نويسنده , , Hal M. Hoffman، نويسنده , , Veronika Person، نويسنده , , Ilka Lorenzen-Schmidt، نويسنده , , Marie-Louise Bang، نويسنده , , Takeharu Hayashi، نويسنده , , Nobuyuki Shiga، نويسنده , , Hideo Yasukawa، نويسنده , , Wolfgang Schaper، نويسنده , , William McKenna، نويسنده , , Mitsuhiro Yokoyama، نويسنده , , Nicholas J. Schork، نويسنده , , Jeffrey H. Omens، نويسنده , , Andrew D. McCulloch ، نويسنده , , Akinori Kimura، نويسنده , , Carol C. Gregorio، نويسنده , , Wolfgang Poller، نويسنده , , Jutta Schaper، نويسنده , , Heinz P. Schultheiss، نويسنده , , et al.، نويسنده ,
Abstract :
Muscle cells respond to mechanical stretch stimuli by triggering downstream signals for myocyte growth and survival. The molecular components of the muscle stretch sensor are unknown, and their role in muscle disease is unclear. Here, we present biophysical/biochemical studies in muscle LIM protein (MLP) deficient cardiac muscle that support a selective role for this Z disc protein in mechanical stretch sensing. MLP interacts with and colocalizes with telethonin (T-cap), a titin interacting protein. Further, a human MLP mutation (W4R) associated with dilated cardiomyopathy (DCM) results in a marked defect in T-cap interaction/localization. We propose that a Z disc MLP/T-cap complex is a key component of the in vivo cardiomyocyte stretch sensor machinery, and that defects in the complex can lead to human DCM and associated heart failure.
