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Chehronai Fozil

Summer Research Description: Naked (NKD2) is a vesicular trafficking protein that negatively regulates canonical Wnt signaling and escorts TGF-α to the cell surface of polarized epithelial cells. However, the assorted contents of NKD2 vesicles and their potential to traffic to multiple cellular locations allow NKD2 to exert multiple effects on cells, many of which are undefined. Our study investigates the role of NKD2 vesicular trafficking on the acto-myosin networks’ ability to sense neighboring cell densities and subsequently affect the fates of caco-2 intestinal epithelial cells. Our preliminary immunocytochemistry results showed that the mechanotransduction protein (YAP) was co-localized with NKD2 in the cytoplasm at low cell densities when Nkd2 is overexpressed. In dense polarized Transwell culture, YAP and pYAP were normally localized to the lateral membranes where cells make cell-cell junctions. When NKD2 is overexpressed, YAP and a highly related protein TAZ, were redistributed to the cytoplasm. The expression of the oncoprotein c-MYC was increased in the nucleus under these conditions, which was accompanied by multi-cell layer and lateral lumen phonotypes resembling loss of polarity. We expect knockout of NKD2 using CRISPR-CAS to exert opposite effects on cells. These results suggest that Nkd2 may play crucial role in regulating mechanosensing proteins at cell junctions that control contact inhibition and cell polarity.