Hadp1, a newly identified pleckstrin homology domain protein, is required for cardiac contractility in zebrafish
SUMMARY The vertebrate heart is one of the first organs to form, and its early function and morphogenesis are crucial for continued embryonic development. Here we analyze the effects of loss of Heart adaptor protein 1 (Hadp1), which we show is required for normal function and morphogenesis of the em...
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The Company of Biologists
2011-09-01
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Series: | Disease Models & Mechanisms |
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doaj-70b4d00401de4ceda2f37e882d6634602020-11-25T02:22:00ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112011-09-014560762110.1242/dmm.002204002204Hadp1, a newly identified pleckstrin homology domain protein, is required for cardiac contractility in zebrafishJoshua D. WytheMichael J. JurynecLisa D. UrnessChristopher A. JonesM. Khaled SabehAndreas A. WerdichMariko SatoH. Joseph YostDavid J. GrunwaldCalum A. MacRaeDean Y. LiSUMMARY The vertebrate heart is one of the first organs to form, and its early function and morphogenesis are crucial for continued embryonic development. Here we analyze the effects of loss of Heart adaptor protein 1 (Hadp1), which we show is required for normal function and morphogenesis of the embryonic zebrafish heart. Hadp1 is a pleckstrin homology (PH)-domain-containing protein whose expression is enriched in embryonic cardiomyocytes. Knockdown of hadp1 in zebrafish embryos reduced cardiac contractility and altered late myocyte differentiation. By using optical mapping and submaximal levels of hadp1 knockdown, we observed profound effects on Ca2+ handling and on action potential duration in the absence of morphological defects, suggesting that Hadp1 plays a major role in the regulation of intracellular Ca2+ handling in the heart. Hadp1 interacts with phosphatidylinositol 4-phosphate [PI4P; also known as PtdIns(4)P] derivatives via its PH domain, and its subcellular localization is dependent upon this motif. Pharmacological blockade of the synthesis of PI4P derivatives in vivo phenocopied the loss of hadp1 in zebrafish. Collectively, these results demonstrate that hadp1 is required for normal cardiac function and morphogenesis during embryogenesis, and suggest that hadp1 modulates Ca2+ handling in the heart through its interaction with phosphatidylinositols.http://dmm.biologists.org/content/4/5/607 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Joshua D. Wythe Michael J. Jurynec Lisa D. Urness Christopher A. Jones M. Khaled Sabeh Andreas A. Werdich Mariko Sato H. Joseph Yost David J. Grunwald Calum A. MacRae Dean Y. Li |
spellingShingle |
Joshua D. Wythe Michael J. Jurynec Lisa D. Urness Christopher A. Jones M. Khaled Sabeh Andreas A. Werdich Mariko Sato H. Joseph Yost David J. Grunwald Calum A. MacRae Dean Y. Li Hadp1, a newly identified pleckstrin homology domain protein, is required for cardiac contractility in zebrafish Disease Models & Mechanisms |
author_facet |
Joshua D. Wythe Michael J. Jurynec Lisa D. Urness Christopher A. Jones M. Khaled Sabeh Andreas A. Werdich Mariko Sato H. Joseph Yost David J. Grunwald Calum A. MacRae Dean Y. Li |
author_sort |
Joshua D. Wythe |
title |
Hadp1, a newly identified pleckstrin homology domain protein, is required for cardiac contractility in zebrafish |
title_short |
Hadp1, a newly identified pleckstrin homology domain protein, is required for cardiac contractility in zebrafish |
title_full |
Hadp1, a newly identified pleckstrin homology domain protein, is required for cardiac contractility in zebrafish |
title_fullStr |
Hadp1, a newly identified pleckstrin homology domain protein, is required for cardiac contractility in zebrafish |
title_full_unstemmed |
Hadp1, a newly identified pleckstrin homology domain protein, is required for cardiac contractility in zebrafish |
title_sort |
hadp1, a newly identified pleckstrin homology domain protein, is required for cardiac contractility in zebrafish |
publisher |
The Company of Biologists |
series |
Disease Models & Mechanisms |
issn |
1754-8403 1754-8411 |
publishDate |
2011-09-01 |
description |
SUMMARY
The vertebrate heart is one of the first organs to form, and its early function and morphogenesis are crucial for continued embryonic development. Here we analyze the effects of loss of Heart adaptor protein 1 (Hadp1), which we show is required for normal function and morphogenesis of the embryonic zebrafish heart. Hadp1 is a pleckstrin homology (PH)-domain-containing protein whose expression is enriched in embryonic cardiomyocytes. Knockdown of hadp1 in zebrafish embryos reduced cardiac contractility and altered late myocyte differentiation. By using optical mapping and submaximal levels of hadp1 knockdown, we observed profound effects on Ca2+ handling and on action potential duration in the absence of morphological defects, suggesting that Hadp1 plays a major role in the regulation of intracellular Ca2+ handling in the heart. Hadp1 interacts with phosphatidylinositol 4-phosphate [PI4P; also known as PtdIns(4)P] derivatives via its PH domain, and its subcellular localization is dependent upon this motif. Pharmacological blockade of the synthesis of PI4P derivatives in vivo phenocopied the loss of hadp1 in zebrafish. Collectively, these results demonstrate that hadp1 is required for normal cardiac function and morphogenesis during embryogenesis, and suggest that hadp1 modulates Ca2+ handling in the heart through its interaction with phosphatidylinositols. |
url |
http://dmm.biologists.org/content/4/5/607 |
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