# TEAD-independent mechanisms of YAP function in cardiomyocyte cell cycle reentry

## TL;DR

This study shows that a modified form of YAP can help heart muscle cells divide again, offering a new way to repair heart damage.

## Contribution

The study reveals a TEAD-independent mechanism of YAP in promoting cardiomyocyte cell cycle reentry.

## Key findings

- YAP6SA promotes cardiomyocyte cell cycle reentry without interacting with TEADs.
- YAP6SA interacts with MPDZ to regulate Rho GTPases and cell cycle progression.
- YAP6SA overexpression is well tolerated in mammalian hearts.

## Abstract

This study demonstrates that YAP6SA promotes cardiomyocyte cell cycling through TEAD-independent pathways, suggesting a novel therapeutic approach for heart repair.

Adult mammalian hearts exhibit limited regenerative capacity because of the restricted renewal of cardiomyocytes. Recent studies reveal that mammalian hearts exhibit transient regenerative potential within a short time frame after birth, suggesting a regulatory mechanism that prevents adult hearts from initiating a regenerative response to cardiac injury. Here, we discovered that an active form of YAP, named YAP6SA, which is not inhibited by the Hippo signaling pathway and does not interact with TEADs, induces cardiomyocyte cell cycle reentry. In addition, YAP6SA interacts with scaffold protein MPDZ to regulate Rho GTPases and promote cell cycle progression in cardiomyocytes (CMs). Importantly, YAP6SA overexpression is well tolerated in mammalian hearts. These findings provide new insights into YAP function in cardiomyocytes.