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    K. Simons

    Research Interests:
    A number of in vitro and in vivo studies have shown that the large superfamily of Ras-related low molecular weight GTP-binding proteins includes proteins which are involved in the control of membrane traffic. In the yeast Saccharomyces... more
    A number of in vitro and in vivo studies have shown that the large superfamily of Ras-related low molecular weight GTP-binding proteins includes proteins which are involved in the control of membrane traffic. In the yeast Saccharomyces cerevisiae, the SEC4 gene encodes a 23 Kd ras-related GTP-binding protein involved in the regulation of vesicular traffic from the Golgi apparatus to the plasma membrane. The protein is found associated with both the cytoplasmic surface of the plasma membrane and secretory vesicles (Salminen and Novick, 1987; Goud et al., 1988). Temperature-sensitive and dominant SEC4 mutants lead to a block in transport from the Golgi apparatus and accumulation of post-Golgi secretory vesicles (Salminen and Novick, 1987; Walworth et al., 1989). The YPT1 gene product is a 23 Kd GTP-binding protein (Gallwitz et al., 1983) which functions at an earlier step of the secretory pathway, from the ER to or within the Golgi apparatus (Schmitt et al., 1986; 1988; Segev and Botstein, 1987; Segev et al., 1988; Baker et al, 1990).
    In Madin-Darby canine kidney (MDCK) cells (a polarized epithelial cell line) infected with influenza virus, the hemagglutinin behaves as an aDcal plasma membrane glycoprotein. To determine biochemically the domain on the plasma membrane,... more
    In Madin-Darby canine kidney (MDCK) cells (a polarized epithelial cell line) infected with influenza virus, the hemagglutinin behaves as an aDcal plasma membrane glycoprotein. To determine biochemically the domain on the plasma membrane, apical or basolateral, where newly synthesized hemagglutinin first appears, cells were cultured on Millipore filters to make both cell surface domains independently accessible. Hemagglutinin in virus-infected cells
    Abstract. MDCK cells display fluid-phase transcytosis in both directions across the cell. Transcytosis of cell surface molecules was estimated by electron micro-scopic analysis of streptavidin-gold-labeled frozen sec-tions of biotinylated... more
    Abstract. MDCK cells display fluid-phase transcytosis in both directions across the cell. Transcytosis of cell surface molecules was estimated by electron micro-scopic analysis of streptavidin-gold-labeled frozen sec-tions of biotinylated cells. Within 3 h, •10% of the ...
    Proc. Natl. Acad. Sci. USA Vol. 92, pp. 8655-8659, September 1995 Cell Biology ... De novo formation of caveolae in lymphocytes by expression ofVIP21-caveolin ... ANNA M. FRA, EDWARD WILLIAMSON, KAI SIMONS, AND ROBERT G. PARTON ...... more
    Proc. Natl. Acad. Sci. USA Vol. 92, pp. 8655-8659, September 1995 Cell Biology ... De novo formation of caveolae in lymphocytes by expression ofVIP21-caveolin ... ANNA M. FRA, EDWARD WILLIAMSON, KAI SIMONS, AND ROBERT G. PARTON ... European Molecular Biology ...
    A new aspect of cell membrane structure is presented, based on the dynamic clustering of sphingolipids and cholesterol to form rafts that move within the fluid bilayer. It is proposed that these rafts function as platforms for the... more
    A new aspect of cell membrane structure is presented, based on the dynamic clustering of sphingolipids and cholesterol to form rafts that move within the fluid bilayer. It is proposed that these rafts function as platforms for the attachment of proteins when membranes are moved around inside ...
    In vertebrates, the formation of raft lipid microdomains plays an important part in both polarized protein sorting and signal transduction. To establish a system in which raft-dependent processes could be studied genetically, we have... more
    In vertebrates, the formation of raft lipid microdomains plays an important part in both polarized protein sorting and signal transduction. To establish a system in which raft-dependent processes could be studied genetically, we have analyzed the protein and lipid composition of these microdomains in Drosophila melanogaster. Using mass spectrometry, we identified the phospholipids, sphingolipids, and sterols present in Drosophila membranes. Despite chemical differences between Drosophila and mammalian lipids, their structure suggests that the biophysical properties that allow raft formation have been preserved. Consistent with this, we have identified a detergent-insoluble fraction of Drosophila membranes that, like mammalian rafts, is rich in sterol, sphingolipids, and glycosylphosphatidylinositol-linked proteins. We show that the sterol-linked Hedgehog N-terminal fragment associates specifically with this detergent-insoluble membrane fraction. Our findings demonstrate that raft fo...