Kindlin-2 interacts with α-actinin-2 and β1 integrin to maintain the integrity of the Z-disc in cardiac muscles

FEBS Lett. 2015 Jul 22;589(16):2155-62. doi: 10.1016/j.febslet.2015.06.022. Epub 2015 Jul 2.

Abstract

Kindlin-2, as an integrin-interacting protein, was known to be required for the maintenance of cardiac structure and function in zebrafish. However, the mechanism remains unclear. We found that Kindlin-2 interacts and colocalizes with α-actinin-2 at the Z-disc of mouse cardiac muscles and there Kindlin-2 also interacts with β1 integrin. Knockdown of Kindlin-2 influences the association of β1 integrin with α-actinin-2 and disrupts the structure of the Z-disc and leads to cardiac dysfunction. Our data indicated that Kindlin-2 is a novel α-actinin-2-interacting protein and plays an important role in the regulation of cardiac structure and function.

Keywords: Cardiac structure; Kindlin-2; The Z-disc; α-Actinin-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinin / metabolism*
  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Cytoskeletal Proteins / antagonists & inhibitors
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Glutathione Transferase / genetics
  • Glutathione Transferase / metabolism
  • Integrin beta1 / metabolism*
  • Male
  • Mice, Inbred ICR
  • Muscle Proteins / antagonists & inhibitors
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Myocardial Contraction
  • Myocardium / cytology
  • Myocardium / metabolism*
  • Myocardium / ultrastructure
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / ultrastructure
  • Protein Transport
  • RNA Interference
  • Rats, Sprague-Dawley
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Sarcomeres / metabolism*
  • Sarcomeres / ultrastructure
  • Stroke Volume
  • Ultrasonography
  • Ventricular Dysfunction / diagnostic imaging
  • Ventricular Dysfunction / etiology
  • Ventricular Dysfunction / metabolism

Substances

  • Actn2 protein, mouse
  • Actn2 protein, rat
  • Cytoskeletal Proteins
  • Integrin beta1
  • Muscle Proteins
  • Recombinant Fusion Proteins
  • kindlin-2 protein, mouse
  • Actinin
  • Glutathione Transferase