Murine Creld1 controls cardiac development through activation of calcineurin/NFATc1 signaling

Mass, Elvira; Wachten, Dagmar; Aschenbrenner, Anna C.; Voelzmann, André; Hoch, Michael

Abstract

Calcineurin is a heteromeric Ca²⁺-dependent serine/threonine phosphatase. It dephosphorylates the transcription factor nuclear factor of activated Tcells (NFAT) in the cytoplasm, which subsequently undergoes nuclear translocation. NFAT regulates numerous biological processes, including inflammatory Tcell responses and cardiac development. Our study identifies the Cysteine-Rich with EGF-Like Domains 1 (Creld1) gene as a regulator of calcineurin/NFATc1 signaling. We show that Creld1 is sufficient to promote NFATc1 dephosphorylation and translocation to the nucleus. Creld1 is contained in a joint protein complex with the regulatory subunit of calcineurin, CnB, thereby controlling calcineurin function. Localization of Creld1 at the endoplasmic reticulum (ER) is important to exert its action on calcineurin. By using Creld1KO mice, we demonstrate that Creld1 is essential for heart development. Creld1 function is required for the VEGF-dependent proliferation of endocardial cells by promoting the expression of NFATc1 target-genes. Collectively, our study identifies Creld1 as an important regulator of calcineurin/NFATc1 signaling. © 2014 Elsevier Inc.

Citation

Mass, E., Wachten, D., Aschenbrenner, A. C., Voelzmann, A., & Hoch, M. (2014). Murine Creld1 controls cardiac development through activation of calcineurin/NFATc1 signaling. Developmental Cell, 28(6), 711-726. https://doi.org/10.1016/j.devcel.2014.02.012

• Journal Article Type: Article
• Acceptance Date: Feb 13, 2014
• Online Publication Date: Mar 31, 2014
• Publication Date: Mar 31, 2014
• Deposit Date: Feb 8, 2024
• Journal: Developmental Cell
• Print ISSN: 1534-5807
• Electronic ISSN: 1878-1551
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 28
• Issue: 6
• Pages: 711-726
• DOI: https://doi.org/10.1016/j.devcel.2014.02.012
• Public URL: https://hull-repository.worktribe.com/output/4371680