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2012-2013: Proposed research project 05

Roles of membrane lipids in the epithelial-tube morphogenesis
Leader : Junichi Ikenouchi
Research progress

My research project is to elucidate the involvement of membrane lipids in the formation of epithelial polarity and tubulogenesis. Cell polarity, asymmetry in cell shape, protein distributions and functions, exists not only in epithelial cells, but also in single-cell organisms, including budding yeast. Considering that evolutionarily diverse cell types use different sets of polarity proteins, I examined whether evolutionally conserved membrane lipids also function in the formation of cell polarization. As a result, I revealed that sphingomyelins are highly enriched in the microvilli of apical membranes in epithelial cells by using immune-electron microscopy. Depletion of spihingomyelin led to loss of microvilli without affecting apico-basal polarity. Furthermore, I identified Podocalyixin-1 as a sphingomyelin-associated membrane protein and revealed that the protein complex comprised of Podocalyxin-1―EBP-50―PIP5Kbeta is essential for the microvilli (J. Cell Sci., 2013). When sphingomyelin-depleted epithelial cells were grown in a three-dimensional matrix to generate a cyst-like structure, inappropriate positioning of apical surfaces within the cyst occurred (unpublished data).Thus, I demonstrated that spihingomyelins play essential roles in the formation of epithelial polarity and tubulogenesis.