Suppression of Rap1 impairs cardiac myofibrils and conduction system in zebrafish.

Numerous studies have revealed that Rap1 (Ras-proximate-1 or Ras-related protein 1), a small GTPase protein, plays a crucial role in mediating cAMP signaling in isolated cardiac tissues and cell lines. However, the involvement of Rap1 in the cardiac development in vivo is largely unknown. By injecti...

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Main Authors: Wei Dong, Zhenglin Yang, Fan Yang, Jialiang Wang, Yan Zhuang, Chongren Xu, Bo Zhang, Xiao-Li Tian, Dong Liu
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3511394?pdf=render
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spelling doaj-b751b0a9a484404699a97397e94a60832020-11-25T01:25:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01711e5096010.1371/journal.pone.0050960Suppression of Rap1 impairs cardiac myofibrils and conduction system in zebrafish.Wei DongZhenglin YangFan YangJialiang WangYan ZhuangChongren XuBo ZhangXiao-Li TianDong LiuNumerous studies have revealed that Rap1 (Ras-proximate-1 or Ras-related protein 1), a small GTPase protein, plays a crucial role in mediating cAMP signaling in isolated cardiac tissues and cell lines. However, the involvement of Rap1 in the cardiac development in vivo is largely unknown. By injecting anti-sense morpholino oligonucleotides to knock down Rap1a and Rap1b in zebrafish embryos, and in combination with time-lapsed imaging, in situ hybridization, immunohistochemistry and transmission electron microscope techniques, we seek to understand the role of Rap1 in cardiac development and functions. At an optimized low dose of mixed rap1a and rap1b morpholino oligonucleotides, the heart developed essentially normally until cardiac contraction occurred. Morphant hearts showed the myocardium defect phenotypes, most likely due to disrupted myofibril assembly and alignment. In vivo heart electrocardiography revealed prolonged P-R interval and QRS duration, consistent with an adherens junction defect and reduced Connexons in cardiac myocytes of morphants. We conclude that a proper level of Rap1 is crucial for heart morphogenesis and function, and suggest that Rap1 and/or their downstream factor genes are potential candidates for genetic screening for human heart diseases.http://europepmc.org/articles/PMC3511394?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Wei Dong
Zhenglin Yang
Fan Yang
Jialiang Wang
Yan Zhuang
Chongren Xu
Bo Zhang
Xiao-Li Tian
Dong Liu
spellingShingle Wei Dong
Zhenglin Yang
Fan Yang
Jialiang Wang
Yan Zhuang
Chongren Xu
Bo Zhang
Xiao-Li Tian
Dong Liu
Suppression of Rap1 impairs cardiac myofibrils and conduction system in zebrafish.
PLoS ONE
author_facet Wei Dong
Zhenglin Yang
Fan Yang
Jialiang Wang
Yan Zhuang
Chongren Xu
Bo Zhang
Xiao-Li Tian
Dong Liu
author_sort Wei Dong
title Suppression of Rap1 impairs cardiac myofibrils and conduction system in zebrafish.
title_short Suppression of Rap1 impairs cardiac myofibrils and conduction system in zebrafish.
title_full Suppression of Rap1 impairs cardiac myofibrils and conduction system in zebrafish.
title_fullStr Suppression of Rap1 impairs cardiac myofibrils and conduction system in zebrafish.
title_full_unstemmed Suppression of Rap1 impairs cardiac myofibrils and conduction system in zebrafish.
title_sort suppression of rap1 impairs cardiac myofibrils and conduction system in zebrafish.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2012-01-01
description Numerous studies have revealed that Rap1 (Ras-proximate-1 or Ras-related protein 1), a small GTPase protein, plays a crucial role in mediating cAMP signaling in isolated cardiac tissues and cell lines. However, the involvement of Rap1 in the cardiac development in vivo is largely unknown. By injecting anti-sense morpholino oligonucleotides to knock down Rap1a and Rap1b in zebrafish embryos, and in combination with time-lapsed imaging, in situ hybridization, immunohistochemistry and transmission electron microscope techniques, we seek to understand the role of Rap1 in cardiac development and functions. At an optimized low dose of mixed rap1a and rap1b morpholino oligonucleotides, the heart developed essentially normally until cardiac contraction occurred. Morphant hearts showed the myocardium defect phenotypes, most likely due to disrupted myofibril assembly and alignment. In vivo heart electrocardiography revealed prolonged P-R interval and QRS duration, consistent with an adherens junction defect and reduced Connexons in cardiac myocytes of morphants. We conclude that a proper level of Rap1 is crucial for heart morphogenesis and function, and suggest that Rap1 and/or their downstream factor genes are potential candidates for genetic screening for human heart diseases.
url http://europepmc.org/articles/PMC3511394?pdf=render
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