Myofibrils made up of actin and 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 heart, 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 heart and caused disorganization of actin filaments. Electron microscopy of sept7b-depleted larvae showed disorganization of heart myofibrils and partial detachment from Z-discs. 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 (raldh2), which catalyzes the synthesis of retinoic acid (RA), necessary for heart morphogenesis. We further observed that the sept7b and the RA signaling pathways converge to regulate cardiac function. Together, these results specify an essential role for sept7b in the contractile function of the heart.
- septin 7
- Copyright © 2016, American Journal of Physiology-Heart and Circulatory Physiology