PUBLICATION
Sept7b is required for the subcellular organization of cardiomyocytes and cardiac function in zebrafish.
- Authors
- Dash, S.N., Narumanchi, S., Paavola, J., Perttunen, S., Wang, H., Lakkisto, P., Tikkanen, I., Lehtonen, S.
- ID
- ZDB-PUB-170328-9
- Date
- 2017
- Source
- American journal of physiology. Heart and circulatory physiology 312(5): H1085-H1095 (Journal)
- Registered Authors
- Keywords
- actin, differentiation, myofibril, raldh2, septin 7
- MeSH Terms
-
- Actin Cytoskeleton/metabolism*
- Animals
- Morphogenesis/physiology*
- Muscle Cells/physiology*
- Septins/metabolism*
- Subcellular Fractions/metabolism*
- Ventricular Function/physiology*
- Zebrafish/physiology*
- Zebrafish Proteins/metabolism*
- PubMed
- 28341635 Full text @ Am. J. Physiol. Heart Circ. Physiol.
Citation
Dash, S.N., Narumanchi, S., Paavola, J., Perttunen, S., Wang, H., Lakkisto, P., Tikkanen, I., Lehtonen, S. (2017) Sept7b is required for the subcellular organization of cardiomyocytes and cardiac function in zebrafish.. American journal of physiology. Heart and circulatory physiology. 312(5):H1085-H1095.
Abstract
Myofibrils made up of actin, myosin, and associated proteins generate the contractile force in muscle, and, consequently, mutations in these proteins may lead to heart failure. Septins are a conserved family of small GTPases that associate with actin filaments, microtubules, and cellular membranes. Despite the importance of septins in cytoskeleton organization, their role in cardiomyocyte organization and function is poorly characterized. Here, we show that septin 7 is expressed in both embryonic and adult zebrafish hearts and elucidate the physiological significance of sept7b, the zebrafish ortholog of human septin 7, in the heart in embryonic and larval zebrafish. Knockdown of sept7b reduced F-actin and α-cardiac actin expression in the heart and caused disorganization of actin filaments. Electron microscopy of sept7b-depleted larvae showed disorganization of heart myofibrils and partial detachment from Z-disks. Functional studies revealed that knockdown of sept7b leads to reduced ventricular dimensions, contractility, and cardiac output. Furthermore, we found that depletion of sept7b diminished the expression of retinaldehyde dehydrogenase 2, which catalyzes the synthesis of retinoic acid necessary for heart morphogenesis. We further observed that the sept7b and retinoic acid signaling pathways converge to regulate cardiac function. Together, these results specify an essential role for sept7b in the contractile function of the heart.NEW & NOTEWORTHY Knockdown of the zebrafish ortholog of human septin 7 (sept7b) destabilizes cardiac actin and reduces ventricular dimensions, contractility, and cardiac output in larval zebrafish, indicating that sept7b is essential for cardiac function. We further found that sept7b and retinoic acid signaling pathways converge to regulate cardiac function. These data prompt further studies defining the role of sept7b in cardiomyopathies.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping