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

• Kindlin-2 colocalizes with α-actinin-2 at the Z-disc.
• Kindlin-2 interacts with α-actinin-2 and integrin β1.
• Knockdown of Kindlin-2 disrupts the Z-disc structure.
• Knockdown of Kindlin-2 affects cardiac systolic function.

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.