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The cardiac mechanical stretch sensor machinery involves a Z disc complex that is defective in a subset of human dilated cardiomyopathy.

Authors: Knoll, R  Hoshijima, M  Hoffman, HM  Person, V  Lorenzen-Schmidt, I  Bang, ML  Hayashi, T  Shiga, N  Yasukawa, H  Schaper, W  McKenna, W  Yokoyama, M  Schork, NJ  Omens, JH  McCulloch, AD  Kimura, A  Gregorio, CC  Poller, W  Schaper, J  Schultheiss, HP  Chien, KR 
Citation: Knoll R, etal., Cell 2002 Dec 27;111(7):943-55.
Pubmed: (View Article at PubMed) PMID:12507422

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.

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CRRD Object Information
CRRD ID: 734841
Created: 2004-02-03
Species: All species
Last Modified: 2004-02-03
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.