Vps11, a subunit of the tethering complexes HOPS and CORVET, is involved in regulation of glycolipid degradation and retrograde toxin transport.
We recently reported that ERM (ezrin, radixin, moesin) proteins are involved in intracellular sorting of Shiga toxin (Stx) and its receptor globotriaosylceramide (Gb3), and that depletion of ezrin and moesin reduced retrograde Golgi transport of Stx. In the same study, we found that knockdown of Vps11, a core subunit of both the homotypic fusion and protein sorting (HOPS) complex and the class C core vacuole/endosome tethering factor (CORVET), increased retrograde transport of Stx and could counteract the inhibiting effect of moesin and ezrin knockdown. In this study we demonstrate that Vps11 knockdown also leads to increased Stx toxicity as well as increased retrograde transport and toxicity of ricin. Additionally, we show that knockdown of Vps11 restores the reduced Gb3 level observed after moesin depletion.
Department of Biochemistry; Institute for Cancer Research; The Norwegian Radium Hospital; Oslo University Hospital; Montebello, Oslo, Norway ; Department of Biosciences; Faculty of Mathematics and Natural Sciences; University of Oslo; Oslo, Norway ; Centre for Cancer Biomedicine; Faculty of Medicine; University of Oslo; Montebello, Oslo, Norway.
Audun Sverre
AS
Kvalvaag
Department of Biochemistry; Institute for Cancer Research; The Norwegian Radium Hospital; Oslo University Hospital; Montebello, Oslo, Norway ; Centre for Cancer Biomedicine; Faculty of Medicine; University of Oslo; Montebello, Oslo, Norway.
Sascha
S
Pust
Department of Biochemistry; Institute for Cancer Research; The Norwegian Radium Hospital; Oslo University Hospital; Montebello, Oslo, Norway ; Department of Biosciences; Faculty of Mathematics and Natural Sciences; University of Oslo; Oslo, Norway ; Centre for Cancer Biomedicine; Faculty of Medicine; University of Oslo; Montebello, Oslo, Norway.
Kirsten
K
Sandvig
CORVET; ERM proteins; Gb3; HOPS; Shiga toxin; Vps11; moesin; retrograde transport; ricin