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70
Opposing roles of Annexin A1 and A2 in trafficking of
Shiga toxin
Lionel Tcatchoff 1 , Sofia Andersson 1 , Audrun Utskarpen 1, 2 , Volker Gerke 3 , Kirsten Sandvig 1, 2 .
CCB, Department of Biochemistry, The Norwegian Radium Hospital, 0310 Oslo, Norway 1 ,
Department of Molecular Biosciences, University of Oslo, 0316 Oslo, Norway 2 , Institute of
Medical Biochemistry, ZMBE , University of Münster, 48149 Münster, Germany 3
Abstract:
Upon binding to cell surface receptors, the bacterial Shiga toxin (Stx) and the plant toxin ricin
are endocytosed and transported retrogradely from endosomal compartment through Golgi
apparatus to the endoplasmic reticulum. The enzymatically active part is then translocated to
the cytosol where it inactivates protein synthesis. As annexins form a family of calcium and
membrane binding proteins with diverse cellular functions, many of them related to membrane
trafficking, we initiated this study to investigate the role of annexin A1 and A2 in the uptake and
intracellular transport of Stx and ricin. Using several experimental approaches to monitor toxin
trafficking in cancerous cells we have shown that annexin A1 and A2 are not involved in toxin
internalization. However, they take part in retrograde transport of Stx while ricin transport is
not affected by knockdown of annexin A1 or A2. Interestingly, these two members of the annexin
family exert an opposite effect on Stx retrograde trafficking. Indeed, knockdown experiments
suggest that annexin A1 normally works as a negative regulator of retrograde transport from the
endosomes to the Golgi, whereas annexin A2 appears to promote this route of Stx trafficking.