Research On Human Heart Developmental Candidate Gene LRRC10

Cardiovascular diseases have become one of the most serious diseases that threaten human beings. It is a critical prerequisite to understand the normal progress of cardiovascular development and the mechanisms underlying the causes of this kind of diseases.In order to promote our understanding for cardiovascular development and discovery the molecular regulatory mechanisms during this progress, here we investigated LRRC10 which has been reported to be expressed in heart and muscle only.A yeast two-hybrid was performed to identify proteins that interact with LRRC10. From a screen using a GAL4 AD-fused human heart cDNA library and GAL4 BD-fused human LRRC10 as bait, we isolated FHL2 as one of the positive clones. The interaction was confirmed using a GST Pull-Down assay in vitro, and an immunoprecipitation (IP) assay in vivo. FHL2 alone distributes both in the cytoplasm and nucleus but was redistributed to the nucleus when LRRC10 was coexpressed in COS-7 cells.Luciferase assay found that LRRC10 inhibit the transcriptional activate of AP-1, while FHL2 increase c-Jun-dependent transcription by acting as a coactivator of AP-1. Results of IP suggest that LRRC10, FHL2 and c-Jun may form a ternary complex. Conclusion, we identify the interaction of FHL2 with LRRCIO and determined that FHL2 and LRRC10 may form a ternary complex with c-Jun. FHL2 and LRRCIO are confronted with each other to modulator the AP-imediated transcriptional activation. They may be involved in the cardiomyocyte through regulation of AP-1 signaling pathway.