title: SNX1 and SNX2 mediate retrograde transport of Shiga toxin.
abstract: The bacterial toxin Shiga toxin (Stx) is transported retrogradely from early endosomes to the Golgi apparatus on its way to the endoplasmic reticulum (ER) and the cytosol. In this study we explored the functions of the two phosphoinositide binding proteins Sorting nexin 1 (SNX1) and Sorting nexin 2 (SNX2) in endosomal sorting of the toxin. When Vero cells were depleted of either SNX1 or SNX2 by small interfering RNA (siRNA), Stx transport to the trans-Golgi network (TGN) was impaired by > or = 40%, whereas combined depletion of SNX1 and SNX2 gave a total inhibition of approximately 80%. Inhibition of PI(3)P formation by wortmannin resulted in a similar reduction. Thus, although being partly redundant, both SNX1 and SNX2 are required for efficient Stx trafficking to the Golgi apparatus.
authors.affiliation: Institute for Cancer Research, Centre for Cancer Biomedicine, The Norwegian Radium Hospital, Montebello, Oslo, Norway.
authors.forename: Audrun
authors.initials: A
authors.lastname: Utskarpen
authors.forename: Hege H
authors.initials: HH
authors.lastname: Slagsvold
authors.forename: Anne Berit
authors.initials: AB
authors.lastname: Dyve
authors.forename: Sigrid S
authors.initials: SS
authors.lastname: Skånland
authors.forename: Kirsten
authors.initials: K
authors.lastname: Sandvig
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004705:Endocytosis / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D022621:Shiga Toxin / Q000378:metabolism*; D058305:Sorting Nexins; D014709:Vero Cells; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C516568:SNX10 protein, human; C513979:SNX2 protein, human; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins; D022621:Shiga Toxin