Stk38 Modulates Rbm24 Protein Stability to Regulate Sarcomere Assembly in Cardiomyocytes.
RNA-binding protein Rbm24 is a key regulator of heart development and required for sarcomere assembly and heart contractility. Yet, its underlying mechanism remains unclear. Here, we link serine/threonine kinase 38 (Stk38) signaling to the regulation of Rbm24 by showing that Rbm24 phosphorylation and its function could be modulated by Stk38. Using co-immunoprecipitation coupled with mass spectrometry technique, we identified Stk38 as an endogenous binding partner of Rbm24. Stk38 knockdown resulted in decreased Rbm24 protein level in cardiomyocytes. Further studies using Stk38 kinase inhibitor or activator showed that Rbm24 protein stability was regulated in a kinase activity-dependent manner. Deficiency of Stk38 caused reduction of sarcomere proteins and disarrangement of sarcomere, suggesting that Stk38 is essential for Rbm24 to regulate sarcomere assembly. Our results revealed that Stk38 kinase catalyzes the phosphorylation of Rbm24 during sarcomerogensis and this orchestrates accurate sarcomere alignment. This furthers our understanding of the regulatory mechanism of cardiac sarcomere assembly in both physiologic and pathologic contexts, and uncovers a potential novel pathway to cardiomyopathy through modulating the Stk38/Rbm24 protein activity.
The Institute of Stem Cell and Regenerative Medicine, Medical College, Xiamen University, 361100, P.R. China.|Fujian Key Laboratory of Organ and Tissue Regeneration, Medical College, Xiamen University, 361100, P.R. China.
Jing
J
Liu
The Institute of Stem Cell and Regenerative Medicine, Medical College, Xiamen University, 361100, P.R. China.
Xu
X
Kong
Department of Biological Sciences, National University of Singapore, 117543, Singapore.
Yew Mun
YM
Lee
The Institute of Stem Cell and Regenerative Medicine, Medical College, Xiamen University, 361100, P.R. China.
Meng Kai
MK
Zhang
The Institute of Stem Cell and Regenerative Medicine, Medical College, Xiamen University, 361100, P.R. China.
Li Yan
LY
Guo
The Institute of Stem Cell and Regenerative Medicine, Medical College, Xiamen University, 361100, P.R. China.
Yu
Y
Lin
Department of Biological Sciences, National University of Singapore, 117543, Singapore.
Teck Kwang
TK
Lim
Department of Biological Sciences, National University of Singapore, 117543, Singapore.
Qingsong
Q
Lin
The Institute of Stem Cell and Regenerative Medicine, Medical College, Xiamen University, 361100, P.R. China.|Fujian Key Laboratory of Organ and Tissue Regeneration, Medical College, Xiamen University, 361100, P.R. China.
Xiu Qin
XQ
Xu
D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D013058:Mass Spectrometry; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000502:physiology*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012518:Sarcomeres / Q000378:metabolism*; D000099259:N-myc Downstream-Regulated Gene 1 Protein
D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016601:RNA-Binding Proteins; D000099259:N-myc Downstream-Regulated Gene 1 Protein; C547648:Rbm24 protein, mouse