TY - JOUR
T1 - The cardiac mechanical stretch sensor machinery involves a Z disc complex that is defective in a subset of human dilated cardiomyopathy
AU - Knöll, Ralph
AU - Hoshijima, Masahiko
AU - Hoffman, Hal M.
AU - Person, Veronika
AU - Lorenzen-Schmidt, Ilka
AU - Bang, Marie Louise
AU - Hayashi, Takeharu
AU - Shiga, Nobuyuki
AU - Yasukawa, Hideo
AU - Schaper, Wolfgang
AU - McKenna, William
AU - Yokoyama, Mitsuhiro
AU - Schork, Nicholas J.
AU - Omens, Jeffrey H.
AU - McCulloch, Andrew D.
AU - Kimura, Akinori
AU - Gregorio, Carol C.
AU - Poller, Wolfgang
AU - Schaper, Jutta
AU - Schultheiss, Heinz P.
AU - Chien, Kenneth R.
N1 - Funding Information:
Drs. S. Labeit and G. Faulkner are gratefully acknowledged for providing their T-cap antibodies. The Resource Center is acknowledged for providing the MLP encoding genomic clones in support of R. Knöll. R. Knöll is supported by DFG Kn 448/2-1, DFG Kn 448/6-1. K. Jung is acknowledged for assistance with a portion of the PCR based patient analyses. N. Dalton is acknowledged for help in performing the echocardiography. Dr. H. Fechner is acknowledged for his support in genotyping and sequencing. G. Knöll, J. Q. Anderson, S. Woodward, and K. Weldy are acknowledged for their technical assistance. We thank the participating families and Prof. H.P. Schultheiss and Prof. M. Yokoyama for their support of this study. This work was entirely supported by the LeDucq Foundation. This study is dedicated to honor the memory and vision of Jean LeDucq.
PY - 2002/12/27
Y1 - 2002/12/27
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0037184992&partnerID=8YFLogxK
U2 - 10.1016/S0092-8674(02)01226-6
DO - 10.1016/S0092-8674(02)01226-6
M3 - Article
C2 - 12507422
AN - SCOPUS:0037184992
SN - 0092-8674
VL - 111
SP - 943
EP - 955
JO - Cell
JF - Cell
IS - 7
ER -