title: The ERM proteins ezrin and moesin regulate retrograde Shiga toxin transport.
abstract: The ERM proteins (ezrin, radixin and moesin) are known for connecting the actin cytoskeleton to the plasma membrane. They have been found to associate with lipid rafts as well as to be important for endosomal sorting and receptor signaling. However, little is known about the role of ERM proteins in retrograde transport and lipid homeostasis. In this study, we show that ezrin and moesin are important for efficient cell surface association of Shiga toxin (Stx) as well as for its retrograde transport. Furthermore, we show that depletion of these proteins influences endosomal dynamics and seems to enhance Stx transport toward lysosomes. We also show that knockdown of Vps11, a subunit of the HOPS complex, leads to increased retrograde Stx transport and reverses the inhibiting effect of ezrin and moesin knockdown. Importantly, retrograde transport of the plant toxin ricin, which binds to both glycolipids and glycoproteins with a terminal galactose, seems to be unaffected by ezrin and moesin depletion.
authors.affiliation: Department of Biochemistry, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0379, Oslo, Norway.
authors.forename: Audun Sverre
authors.initials: AS
authors.lastname: Kvalvaag
authors.forename: Sascha
authors.initials: S
authors.lastname: Pust
authors.forename: Kristine Ingrid
authors.initials: KI
authors.lastname: Sundet
authors.forename: Nikolai
authors.initials: N
authors.lastname: Engedal
authors.forename: Roger
authors.initials: R
authors.lastname: Simm
authors.forename: Kirsten
authors.initials: K
authors.lastname: Sandvig
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012276:Ricin / Q000235:genetics / Q000378:metabolism; D022621:Shiga Toxin / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism; D000099149:Ezrin
chemical_list: D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D011994:Recombinant Proteins; D012276:Ricin; D022621:Shiga Toxin; D033921:Vesicular Transport Proteins; D000099149:Ezrin; C424438:VPS11 protein, human; C071058:moesin