Main scientific contributions

Detailed studies of toxin interactions (number of binding sites/affinities) with cell surface receptors (Sandvig et al., J. Biol. Chem. 251 (1976) 3977-3984).

Discovery of recycling of endocytosed ligands, shown by using ricin (Sandvig et al., Exp. Cell Res. 21 (1979) 15-25).

Discovery of low pH-induced  translocation of diphtheria toxin across the membrane and that this is associated with a conformational change in the toxin molecule (Sandvig and Olsnes, J. Cell Biol. 87 (1980) 828-832; Sandvig and Olsnes, J. Biol. Chem. 256 (1981) 9068-9076), Sandvig et al., J. Cell Biol. 98 (1984) 963-970) and formation of cation-selective channels in cells (Sandvig and Olsnes, J. Biol. Chem. 263 (1988) 12352-12359). Also deletion mutants can form channels (Stenmark et al. EMBO J. 8 (1989) 2849-2853).

Discovery of requirements (permeable anions, pH-gradient) for diphtheria toxin translocation into cells (Sandvig and Olsnes, J. Cell Physiol. 119 (1984) 7-14; Sandvig and Olsnes J. Biol. Chem. 261 (1986) 1570-1575; Sandvig et al., J. Biol. Chem. 261 (1986)11639-11644), and intermediate stages of toxin translocation (Madshus et al., J. Biol. Chem. 269 (1994) 4648-4652).

Discovery of the requirement for endocytosis of several of the toxins before entry into the cytosol (Sandvig and Olsnes, J. Biol. Chem. 257 (1982) 7495-7503 and J. Biol. Chem. 257 (1982) 7504-7513).

Entry mechanism of picornavirus and the resemblance to toxin uptake (Madshus et al., J. Cell Biol. 98 (1984)1194-1200; EMBO J. 3 (1984) 1945-1950; Virology 139 (1984) 346-357).

Discovery of ricin and ricin-conjugate transport to the Golgi apparatus and the importance of this transport for intoxication (van Deurs et al., J. Cell Biol. 102 (1986) 37-47; van Deurs et al., J. Cell Biol. 102 (1986) 37-47; Sandvig et al., Cancer Res. 46 (1986) 6418-6422; Sandvig et al., J. Cell Biol. 115 (1991) 971-981).

Demonstration of clathrin-independent pathways of endocytosis (Sandvig et al., J. Cell Biol. 105 (1987) 679-689; J. Cell. Biochem. 36 (1988) 73-81), and the selective regulation of this pathway (Sandvig and van Deurs, J. Biol. Chem. 265 (1990) 6382-6388). The clathrin-independent pathway leads to early endosomes (Hansen et al., J. Cell Biol. 123 (1993) 1755-1760).

Discovery that endocytosis of a lipid-binding ligand, Shiga toxin, can occur from clathrin-coated pits (Sandvig et al., J. Cell Biol. 108 (1989) 1331-1343; Sandvig et al., J. Cell Biol. 113 (1991) 553-562).

Transport in polarized epithelial cells: Protein toxins are transcytosed across an epithelial cell layer and their endocytosis and transcytosis is under regulation (Melby et al., J. Cell. Biochem. 47 (1990) 251-260; Eker et al., J. Biol. Chem. 269 (1994) 18607-18615; Prydz et al., J. Cell Biol. 119 (259-272; Llorente et al., J. Cell Sci. 113 (2000) 1213-1221). Their effect is dependent on the side of the epithelium from where they enter (Melby et al., Cancer Res. 53 (1993) 1755-1760. Rho A was found to regulate apical clathrin-independent endocytosis (Garred et al., Traffic 2 (2001) 26-36).

Discovery of retrograde transport of Shiga toxin from the cell surface to the Golgi apparatus and retrogradely to the ER and the nuclear envelope (Sandvig et al., Nature 358 (1992) 510-512; Sandvig et al., J. Cell Biol. 126 (1994) 53-64). Sandvig et al., Mol. Biol. Cell 7 (1996) 1391-1404). This was the first demonstration that a molecule can follow such a pathway.

Demonstration of activation of Shiga toxin by the cellular enzyme furin (Garred et al., J. Biol. Chem. 270 (1995) 10817-10821).

First demonstration of retrograde transport of cholera toxin to the ER (Sandvig et al., Proc. Natl. Acad. Sci. USA 93 (1996) 12339-12343).

Dynamin has an intracellular effect: inhibition of endosome to Golgi transport (Llorente et al., J. Cell Biol. 140 (1998) 553-563; Nicoziani et al., Mol. Biol. Cell 11 (2000) 481-495).

Discovery that a GPI-linked molecule is endocytosed independently of clathrin-coated vesicles and caveolae (Skretting et al., J. Cell Sci. 112 (1999) 3899-3909).

Discovery of a role for cholesterol in clathrin-dependent endocytosis (Rodal et al., Mol. Biol. Cell 10 (1999) 961-974), in macropinocytosis (Grimmer et al., J. Cell Sci. 115 (2002) 2953-2962), and in endosome to Golgi transport (Grimmer et al., Mol. Biol. Cell 11 (2000) 4205-4216).

Formation of clathrin-coated pits with dynamin rings in intact cells (Iversen et al., Proc. Natl. Acad. Sci. USA 100 (2003) 5175-5180).

Induction of direct endosome to ER transport of toxin (Llorente et al., J. Biol. Chem. 278 (2003) 35850-35855).

Characterization of endosome to Golgi transport of toxins (Iversen et al., Mol. Biol. Cell 12 (2001) 2099-2107; Lauvrak et al., J. Cell Sci. 115(2002)3449-3456; Birkeli et al., J. Biol. Chem. 278(2003) 1991-1997; Lauvrak et al., J. Cell Sci. 117 (2004) 2321-2331; Utskarpen et al. Traffic, 7 (2006) 663-672; Skånland et al. Traffic 8 (2007) 297-309; Torgersen et al. J. Biol. Chem. 282 (2007) 16317-16328; Wälchli et al. Mol. Biol. Cell 19 (2008) 95-104; Skånland et al. Cell. Microbiol. 11 (2009) 796-807; PloS ONE 4 (2009) e5935; Raa et al. Traffic 10 (2009) 868-882; Dyve et al. Biochem. Biophys. Res. Commun. 390 (2009) 109-114; Pust et al. PloS ONE 5 (2010) e8844; Pust et al. PloS ONE 5 (2010) e8844; Lingelem et al., Traffic 13 (2012) 443-454); Dang et al., Traffic, 12(2011) 1417-1431; Klokk et al., Toxins 3(2011) 1203-1219; Lingelem et al., Traffic, 13(2012) 443-454; Tcatchoff et al., PloS ONE 7 (2012) e40429; Kvalvaag et al., Traffic 14 (2013) 839-852).

Characterization of ER to cytosol translocation of toxin (Slominska-Wojewodska et al. Mol. Biol. Cell 17 (2006) 1664-1675; Sokolowska et al., Biochem. J. 436 (2011) 371-385); Gregers et al., Toxins 5 (2013) 969-982; Slominska-Wojewodska et al., Biochem. J. 457 (2014) 485-496).

Shiga toxin can although it binds to a glycolipid induce its own endocytosis by signaling through Syk activation and clathrin phosphorylation (Lauvrak et al. Mol. Biol. Cell 17 (2006) 1096-1109; Wälchli et al. Cell Signalling 21 (2009) 1161-1168. No evidence for flotillin in its uptake (Pust et al. PloS ONE 5 (2010) e8844. Importantly Shiga toxin increases the number of clathrin coats at the cell surface (Utskarpen et al. PloS ONE 5 (2010) e10944).

Discussion about the use of Shiga toxin in targeted cancer therapy and imaging (Engedal et al., Micr. Biotechnol. 4 (2011) 32-46).

Prognostic markers: Flotillins are regulators of ErbB2 levels and may be used as prognostic markers (Pust et al., Oncogene 32 (2013) 3443-3451; Asp et al., Oncotarget 7 (2016) 25443-25460). Proteins in urine exosomes from prostate cancer patients (Øverbye et al., Oncotarget 6 (2015) 30357-30376).

Specific lipids affect endocytosis and intracellular transport (Grimmer et al., Traffic  6 (2005) 144-156; Grimmer et al., Traffic 7 (2006) 1243-1253; Llorente et al., Eur. J. Cell Biol. 86 (2007) 405-415; Raa et al., Traffic 10 (2009) 868-882; Bergan et al., Cell. Mol. Life Sci. 71 (21) 4285-300).

Cell density and 2-deoxy-glucose affect retrograde transport (Kavaliauskiene et al., Cell. Mol. Life Sci. 71 (2014) 1097-1116; Kavaliauskiene et al., Biochem. J. 470 (2015) 23-37).

The group exploits its background to study nanoparticles (Tekle et al., Nano Letters 8 (2008) 1858-1865; Skotland et al., Nanomedicine NBM 6 (2010) 730-737; Iversen et al., Nano Today 6 (2011) 176-185; Skotland et al., ASC Nano 5(2011) 7690; Ilina et al., J. Control Release 163 (2012) 385-395; Iversen et al., J. Nanobiotechnol. 10 (2012) 1-11; Skotland et al., Nanomedicine (London) 9 (2014) 1295-1299).

Our competence is used to study exosomes, their composition, release and lipid sorting (Sandvig and Llorente Mol. Cell. Proteomics 2012 PMID: 22457534; Hessvik et al., Biochim. Biophys. Acta 1810 (2012) 1154-1163; Hessvik et al., Frontiers in Genetics 4 (2013) art 36, 1-9; Llorente et al., Biochim. Biophys. Acta 1831 (2013) 1302-1309; Phuyal et al., J. Biol. Chem. 290 (2014) 4225-4237; Phuyal et al., FEBS J., 281 (2014) 2214-2227; Øverbye et al., Oncotarget 6 (2015) 30357-30376; Hessvik et al., Cell. Mol. Life Sci. (2016), in press).

Studies of exosomes resulted in hypothesis of interactions between membrane leaflets (Llorente et al., Biochim. Biophys. Acta 1831 (2013)1302-1309; Phuyal et al., J. Biol. Chem. 290 (2014) 4225-4237; Róg et al., Biochim. Biophys. Acta, 1858 (2015) 281-288; Róg et al., Data in Brief 7 (2016) 1171-1174).

Addition of an ether lipid precursor to cells affects the lipidome, and the data indicate a coupling between metabolism of ether lipids and glycosphingolipids (Bergan et al., PLoS One, 8 (2013) e75904; Phuyal et al., J. Biol. Chem. 290 (2014) 4225-4237).

The first comprehensive and time-resolved measurement of sphingolipid turnover and dynamics in cells using stable isotope-tracer lipidomics (Skotland et al., J. Mol. Biol. (2016) in press).

 
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