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Hadp1, a newly identified pleckstrin homology domain protein, is required for cardiac contractility in zebrafish.
- Source :
-
Disease models & mechanisms [Dis Model Mech] 2011 Sep; Vol. 4 (5), pp. 607-21. Date of Electronic Publication: 2011 May 31. - Publication Year :
- 2011
-
Abstract
- 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 Ca(2+) handling and on action potential duration in the absence of morphological defects, suggesting that Hadp1 plays a major role in the regulation of intracellular Ca(2+) 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 Ca(2+) handling in the heart through its interaction with phosphatidylinositols.
- Subjects :
- 1-Phosphatidylinositol 4-Kinase metabolism
Animals
Body Patterning
Bradycardia embryology
Bradycardia physiopathology
Calcium Signaling
Cardiac Output
Cell Count
Embryo, Nonmammalian metabolism
Embryo, Nonmammalian pathology
Gene Expression Regulation, Developmental
Gene Knockdown Techniques
HEK293 Cells
Heart embryology
Heart physiology
Humans
Muscle Proteins deficiency
Muscle Proteins genetics
Myocytes, Cardiac metabolism
Myocytes, Cardiac pathology
Organogenesis
Protein Binding
Protein Structure, Tertiary
Subcellular Fractions metabolism
Zebrafish embryology
Zebrafish genetics
Zebrafish Proteins deficiency
Zebrafish Proteins genetics
Muscle Proteins chemistry
Muscle Proteins metabolism
Myocardial Contraction physiology
Zebrafish metabolism
Zebrafish Proteins chemistry
Zebrafish Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1754-8411
- Volume :
- 4
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Disease models & mechanisms
- Publication Type :
- Academic Journal
- Accession number :
- 21628396
- Full Text :
- https://doi.org/10.1242/dmm.002204