2026-08-05 コペンハーゲン大学（UCPH）
“The mechanism provides a unifying explanation for diseases that we have previously struggled to understand,” explains Søren Tvorup Christensen, Professor of cell biology and one of the authors of a new paper detailing the mechanism. Illustration: University of Copenhagen
＜関連情報＞
- https://news.ku.dk/all_news/2026/08/researchers-uncover-hidden-mechanism-behind-congenital-heart-disease/
- https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003902
TAK1は、非典型的なTGFB/BMPシグナル伝達において一次繊毛で働き、心臓発生を制御する TAK1 operates at the primary cilium in non-canonical TGFB/BMP signaling to control heart development
Canan Doganli,Oskar Kaaber Thomsen,Daniel A. Baird,Yeasmeen Ali,Menachem V. K. Sarusie,Enrique Audain,Line Jeanett Jessen,Pauline Munck Truelsen,Johanne Bay Mogensen,Maria Schrøder Holm,Kateřina Apolínová,Lorenzo Buttò,Maria Diamanti, [ … ],Lars Allan Larsen
PLOS Biology Published: August 4, 2026
DOI:https://doi.org/10.1371/journal.pbio.3003902
Abstract
Pathogenic variants in the genes encoding the non-canonical TGFB signaling components TAK1 (MAP3K7), TAB2 and PKA-Cα (PRKACA) cause rare multisystem disorders, which may include congenital heart disease (CHD). To investigate the role of TAK1 signaling in CHD, we performed genetic analysis of CHD patients and discovered an increased burden of rare TAB2 and TAK1 variants in patients with extracardiac abnormalities. To address the mechanism of TAK1 in heart development, we performed experiments in cell and animal models. Zebrafish tak1 and tab2 mutants presented with cardiac and extracardiac developmental defects, and tak1 mutant hearts showed downregulation of genes encoding core cardiac transcription factors, sarcomeric proteins and extracellular matrix proteins. In vitro experiments indicated that TAK1 via TAB2 and PKA-Cα is activated at the primary cilium during cardiomyogenesis; activation at this site is enhanced by TGFB/BMP ligands. Inactivation of TAK1 inhibited ciliary signaling and cardiomyocyte differentiation, and patient-derived TAK1 variants reduced its ciliary localization. In conclusion, our data establish a pivotal role for TAK1 and its upstream regulators at the primary cilium in heart development and syndromic CHD.
