Related Experiment Videos
Function of FK506 binding protein (FKBP) in chick embryonic cardiac development
Insights
FKBP12 (FK506 binding protein 12) is crucial for cardiac development, regulating cell proliferation and calcium handling. Its suppression is lethal in early embryos, highlighting its vital role in heart formation.
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- Developmental Biology
Background:
- FKBP12 (FK506 binding protein 12) is an immunophilin involved in intracellular signaling pathways.
- It interacts with ryanodine receptors, IP3 Ca2+ channels, TGF-beta receptor, and CDK, influencing cell proliferation.
- Its specific role in cardiac development requires elucidation.
Purpose of the Study:
- To investigate the temporal expression and regulation of FKBP12 in chick heart development.
- To understand the functional significance of FKBP12 in cardiomyocytes and embryonic heart formation.
Main Methods:
- Analysis of FKBP12 expression in chick embryos and cultured cardiomyocytes.
- Immunohistochemical localization of FKBP12.
- Administration of FK506 to suppress FKBP12 activity in vivo and in vitro.
- Assessment of cardiac morphology, protein levels, and cell proliferation.
Main Results:
- FKBP12 is expressed early in chick embryos (day 4), predominantly in cardiomyocytes and osteo-chondrocytes.
- Cardiac FKBP12 levels increase with development and correlate with SERCA2, not sarcomeric proteins.
- FK506 administration is lethal in early embryos (< day 8) and causes cardiomegaly later.
- In cultured cardiomyocytes, FK506 reduces contractile proteins and inhibits proliferation.
Conclusions:
- FKBP12 is enriched in cell types involved in dynamic calcium handling.
- FKBP12 plays a critical role in cardiac development, likely through modulation of cellular calcium handling.
- Its function is essential for cardiomyocyte proliferation and maintaining cardiac structure.
Abstract:
FK506 binding protein (BP) 12, an immunophilin of FK506-binding proteins, is involved in intra-cellular signal transduction through the calcineurin-nuclear factor pathway. FKBP12 is reported to be associated with the ryanodine-receptor and IP3 Ca2+ channels, and to regulate cell proliferation via binding transforming growth factor (TGF)-beta receptor and cyclin dependent kinase (CDK). To elucidate the function of FKBP12 in cardiac development, we analyzed the temporal profile and regulation of FKBP12 expression in chick heart and in cultured cardiomyocytes. FKBP12 is expressed in embryos as early as day 4 and is predominantly associated with cardiomyocytes and osteo-chondrocytes. Tissue FKBP level in the heart increases with development. Immunohistochemically, the distribution and levels of FKBP12 appear to be related to sarco-endoplasmic reticulum Ca-ATPase 2 (SERCA2) but not to sarcomeric proteins. In proliferating cells, FKBP12 expression correlates with cellular mitosis, but not with DNA synthesis. In earlier embryos (< day 8), suppressing the activity of FKBP by FK506 administration is lethal, and induces cardiomegaly at later stages. In cultured cardiomyocytes, FK506 reduces the level of contractile proteins and inhibits cell proliferation. These results show that FKBP12 is enriched in cell types involved in dynamic Ca handling, and is likely an important molecule for cardiac development. FKBP12 most likely functions by affecting cellular Ca handling, since its effects are modified by modulators of Ca handling by sarcoplasmic reticulum.