Hippo-Yap Signaling Maintains Sinoatrial Node Homeostasis

Authors

Mingjie Zheng
Rich G Li
Jia Song
Xiaolei Zhao
Li Tang
Shannon Erhardt
Wen Chen
Bao H Nguyen
Xiao Li
Min Li
Jianxin Wang
Sylvia M Evans
Vincent M Christoffels
Na Li
Jun Wang

Publication Date

11-29-2022

Journal

Circulation

Abstract

BACKGROUND: The sinoatrial node (SAN) functions as the pacemaker of the heart, initiating rhythmic heartbeats. Despite its importance, the SAN is one of the most poorly understood cardiac entities because of its small size and complex composition and function. The Hippo signaling pathway is a molecular signaling pathway fundamental to heart development and regeneration. Although abnormalities of the Hippo pathway are associated with cardiac arrhythmias in human patients, the role of this pathway in the SAN is unknown.

METHODS: We investigated key regulators of the Hippo pathway in SAN pacemaker cells by conditionally inactivating the Hippo signaling kinases

RESULTS: We found that

CONCLUSIONS: We reveal, for the first time to our knowledge, that the canonical Hippo-Yap pathway plays a pivotal role in maintaining SAN homeostasis.

Keywords

Humans, Mice, Animals, Adaptor Proteins, Signal Transducing, Cell Cycle Proteins, Transforming Growth Factor beta3, Phosphoproteins, Sinoatrial Node, Calcium, Ryanodine Receptor Calcium Release Channel, Protein Serine-Threonine Kinases, Homeostasis, Fibrosis, Cell Proliferation, Tumor Suppressor Proteins

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Associated Data

PMID: 36317529