FAT1 (FAT atypical cadherin 1)

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Specificity & Comments

The FAT proteins are members of the Cadherin superfamily homologous to the Drosophila Fat protein that functions as a positive regulator of planar cell polarity in the Drosophila wing. FAT1 is an unusual cadherin that controls cell growth and planar polarity while acting as a tumor suppressor. FAT1 is a proximal element of a signaling pathway that determines both cellular polarity in the plane of the monolayer and directed actin-dependent cell motility. FAT1 is localized at the leading edge of lamellipodia, filopodia and microspike tips where it directly interacts with Ena/VASP proteins to regulate the actin polymerization complex. When targeted to mitochondrial outer leaflets, the cytoplasmic domain of FAT1 recruits components of the actin polymerization machinery sufficient to induce ectopic actin polymerization. FAT1 expression in vascular smooth muscle cells (VSMCs) increases significantly after arterial injury or growth factor stimulation, implicating FAT1 in the control of VSMC functions central to vascular remodeling by facilitating migration and limiting proliferation. FAT1 is also involved in psychic disorders, and its action may be of patho-physiological importance.