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ZFIN ID: ZDB-PUB-140127-25
3-OST-7 regulates BMP-dependent cardiac contraction
Samson, S.C., Ferrer, T., Jou, C.J., Sachse, F.B., Shankaran, S.S., Shaw, R.M., Chi, N.C., Tristani-Firouzi, M., and Yost, H.J.
Date: 2013
Source: PLoS Biology 11(12): e1001727 (Journal)
Registered Authors: Chi, Neil C., Shankaran, Sunita Sathy, Yost, H. Joseph
Keywords: Embryos, Cardiac ventricles, Heart, BMP signaling, Muscle contraction, Myocardium, Zebrafish, Cardiac atria
MeSH Terms:
  • Action Potentials/physiology
  • Animals
  • Bone Morphogenetic Proteins/physiology*
  • Gene Knockdown Techniques
  • Muscle Development/physiology
  • Myocardial Contraction/physiology*
  • Myocytes, Cardiac/physiology
  • Sarcomeres/physiology
  • Signal Transduction/physiology
  • Sulfotransferases/physiology*
  • Tropomyosin/physiology
  • Zebrafish
  • Zebrafish Proteins/physiology*
PubMed: 24311987 Full text @ PLoS Biol.
FIGURES
ABSTRACT

The 3-O-sulfotransferase (3-OST) family catalyzes rare modifications of glycosaminoglycan chains on heparan sulfate proteoglycans, yet their biological functions are largely unknown. Knockdown of 3-OST-7 in zebrafish uncouples cardiac ventricular contraction from normal calcium cycling and electrophysiology by reducing tropomyosin4 (tpm4) expression. Normal 3-OST-7 activity prevents the expansion of BMP signaling into ventricular myocytes, and ectopic activation of BMP mimics the ventricular noncontraction phenotype seen in 3-OST-7 depleted embryos. In 3-OST-7 morphants, ventricular contraction can be rescued by overexpression of tropomyosin tpm4 but not by troponin tnnt2, indicating that tpm4 serves as a lynchpin for ventricular sarcomere organization downstream of 3-OST-7. Contraction can be rescued by expression of 3-OST-7 in endocardium, or by genetic loss of bmp4. Strikingly, BMP misregulation seen in 3-OST-7 morphants also occurs in multiple cardiac noncontraction models, including potassium voltage-gated channel gene, kcnh2, affected in Romano-Ward syndrome and long-QT syndrome, and cardiac troponin T gene, tnnt2, affected in human cardiomyopathies. Together these results reveal 3-OST-7 as a key component of a novel pathway that constrains BMP signaling from ventricular myocytes, coordinates sarcomere assembly, and promotes cardiac contractile function.

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