Pathways followed by protein toxins into cells

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Abstract

A number of protein toxins have an enzymatically active part, which is able to modify a cytosolic target. Some of these toxins, for instance ricin, Shiga toxin and cholera toxin, which we will focus on in this article, exert their effect on cells by first binding to the cell surface, then they are endocytosed, and subsequently they are transported retrogradely all the way to the ER before translocation of the enzymatically active part to the cytosol. Thus, studies of these toxins can provide information about pathways of intracellular transport. Retrograde transport to the Golgi and the ER seems to be dependent not only on different Rab and SNARE proteins, but also on cytosolic calcium, phosphatidylinositol 3-kinase and cholesterol. Comparison of the three toxins reveals differences indicating the presence of more than one pathway between early endosomes and the Golgi apparatus or, alternatively, that transport of different toxin-receptor complexes present in a certain subcompartment is differentially regulated.

References (57)

  • S.P. Andreoli et al.

    Hemolytic uremic syndrome: epidemiology, pathophysiology, and therapy

    Pediatr. Nephrol.

    (2002)
  • L. Bai et al.

    Effect of cholesterol/phospholipid ratio on stimulatory GTP-binding protein function

    Biochem. Mol. Biol. Int.

    (1998)
  • S.D. Conner et al.

    Regulated portals of entry into the cell

    Nature

    (2003)
  • H. Damke et al.

    Induction of mutant dynamin specifically blocks endocytic coated vesicle formation

    J. Cell Biol.

    (1994)
  • J.M. Duran et al.

    Myosin motors and not actin comets are mediators of the actin-based Golgi-to-endoplasmic reticulum protein transport

    Mol. Biol. Cell

    (2003)
  • T. Falguieres et al.

    Targeting of shiga toxin b-subunit to retrograde transport route in association with detergent-resistant membranes

    Mol. Biol. Cell

    (2001)
  • A.E. Frankel et al.

    Targeted toxins

    Clin. Cancer Res.

    (2000)
  • A. Girod et al.

    Evidence for a COP-I-independent transport route from the Golgi complex to the endoplasmic reticulum

    Nat. Cell Biol.

    (1999)
  • S. Grimmer et al.

    Endosome to Golgi transport of ricin is regulated by cholesterol

    Mol. Biol. Cell

    (2000)
  • T. Gura

    Magic bullets hit the target

    Nature.

    (2002)
  • N. Haicheur et al.

    The B subunit of Shiga toxin fused to a tumor antigen elicits CTL and targets dendritic cells to allow MHC class I-restricted presentation of peptides derived from exogenous antigens

    J. Immunol.

    (2000)
  • S.H. Hansen et al.

    Molecules internalized by clathrin-independent endocytosis are delivered to endosomes containing transferrin receptors

    J. Cell Biol.

    (1993)
  • B. Hazes et al.

    Accumulating evidence suggests that several AB-toxins subvert the endoplasmic reticulum-associated protein degradation pathway to enter target cells

    Biochemistry

    (1997)
  • T.-G. Iversen et al.

    Endosome to Golgi transport of ricin is independent of clathrin and of the Rab9- and Rab11-GTPases

    Mol. Biol. Cell

    (2001)
  • T.-G. Iversen et al.

    Formation of clathrin-coated pits with long dynamin-wrapped necks upon inducible expression of antisense to clathrin

    Proc. Natl. Acad. Sci. USA

    (2003)
  • M.E. Jackson et al.

    The KDEL retrieval system is exploited by Pseudomonas exotoxin A, but not by Shiga-like toxin-1, during retrograde transport from the Golgi complex to the endoplasmic reticulum

    J. Cell Sci.

    (1999)
  • L. Johannes et al.

    Facing inward from compartment shores: How many pathways were we looking for?

    Traffic

    (2000)
  • R.J. Kreitman

    Toxin-labeled monoclonal antibodies

    Curr. Pharm. Biotechnol.

    (2001)
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