Endosomal ricin transport: involvement of Rab4- and Rab5-positive compartments.
Transport of the ribosome-inactivating protein ricin through endosomes was studied in A431 cells expressing Rab5-, Rab4-, and Rab11-GFP. It was shown that Rab5- and Rab4-positive functional domains of early endosomes are involved in ricin transport. Ricin enters cells by both clathrin-dependent and clathrin-independent mechanisms. The main pool of internalized toxin accumulates in early endosomes and remains associated with them for a long time. In contrast to earlier observations, current observations indicate that the majority of ricin avoids transport to lysosomes. The low level of ricin association with Rab11 as well as with transferrin accumulated in the pericentriolar recycling compartment shows that the compartment is not responsible for keeping ricin away from degradation in lysosomes. Escape from degradation in lysosomes is assumed to result from the potentiality of ricin to form assemblies within compartments.
Moisenovich
Mihail
M
Biological Faculty, Lomonosov Moscow State University, Vorobjovi gory, 119992, Moscow, Russia.
Tonevitsky
Alex
A
Maljuchenko
Natalia
N
Kozlovskaya
Natalia
N
Agapov
Igor
I
Volknandt
Walter
W
Bereiter-Hahn
Jürgen
J
D045744:Cell Line, Tumor; D002966:Clathrin / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism* / Q000648:ultrastructure; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D018613:Microscopy, Confocal; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012276:Ricin / Q000235:genetics / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D020695:rab4 GTP-Binding Proteins / Q000378:metabolism*; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
D002966:Clathrin; D049452:Green Fluorescent Proteins; D011993:Recombinant Fusion Proteins; D012276:Ricin; D014168:Transferrin; D020691:rab GTP-Binding Proteins; D020695:rab4 GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins