annexin a1 and a2 roles in retrograde trafficking of shiga toxin膜联蛋白a1和a2逆行贩卖志贺毒素的角色.pdfVIP

Annexin A1 and A2: Roles in Retrograde Trafficking of Shiga Toxin 1. 1. 1,2 1 ˚ 1,2 Lionel Tcatchoff , Sofia Andersson , Audrun Utskarpen , Tove Irene Klokk , Sigrid S. Skanland , 1 3 1,2 Sascha Pust , Volker Gerke , Kirsten Sandvig * 1 Department of Biochemistry, Centre for Cancer Biomedicine, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, Oslo, Norway, 2 Department of Molecular Biosciences, University of Oslo, Oslo, Norway, 3 Institute for Medical Chemistry, Center for Molecular Biology of Inflammation, ¨ ¨ University of Munster, Munster, Germany Abstract Annexins constitute a family of calcium and membrane binding proteins. As annexin A1 and A2 have previously been linked to various membrane trafficking events, we initiated this study to investigate the role of these annexins in the uptake and intracellular transport of the bacterial Shiga toxin (Stx) and the plant toxin ricin. Once endocytosed, both toxins are retrogradely transported from endosomes to the Golgi apparatus and the endoplasmic reticulum before being targeted to the cytosol where they inhibit protein synthesis. This study was performed to obtain new information both about toxin transport and the function of annexin A1 and annexin A2. Our data show that depletion of annexin A1 or A2 alters the retrograde transport of Stx but not ricin, without affecting toxin binding or internalization. Knockdown of annexin A1