Pleiotropic effects of afadin, an scaffold molecule, on regulation of cellular functions

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Afadin has pleiotropic cellular functions including cell adhesion, cell migration and cell polarization. However, its molecular mechanisms in these phenomena, especially cell migration and polarization, remain elusive. In this research project, the DIL domain of afadin was found to play pivotal roles in the formation of cell polarity during cell migration. The DIL domain binding molecule ADIP crucially mediated the activation of small G protein Rac. Afadin conditional knockout mice specifically in cardiomyocytes or endothelial cells were generated successfully. From the experiments using these mice, afadin was involved in the progression of cardiac hypertrophy and in the regulation of lymphatic vessel morphology.