Rab11B small GTPase regulates secretion of cysteine proteases in the enteric protozoan parasite Entamoeba histolytica.
Vesicular trafficking plays a pivotal role in the virulence of the enteric protozoan parasite Entamoeba histolytica. In the present study, we showed that one isotype of the small GTPase Rab11, EhRab11B, plays a central role in the secretion of a major virulence factor, cysteine proteases. EhRab11B did not colocalize with markers for the endoplasmic reticulum, early endosomes and lysosomes, but was partially associated with non-acidified vesicles in the endocytic pathway, likely recycling endosomes. Overexpression of EhRab11B resulted in a remarkable increase in both intracellular and secreted cysteine protease activity, concomitant with an augmentation of cytolytic activity as demonstrated by an increased ability to destroy mammalian cells. The oversecretion of cysteine proteases with EhRab11B overexpression was neither sensitive to brefeldin A nor specific to a certain cysteine protease species (e.g. CP1, 2 or 5), suggesting that these three major cysteine proteases are trafficked via an EhRab11B-associated secretory pathway, which is distinct from the classical brefeldin-sensitive pathway. Overexpression of EhRab11B also enhanced exocytosis of the incorporated fluid-phase marker, supporting the notion that it is involved in recycling. This is the first report demonstrating that Rab11 plays a central role in the transport and secretion of pathogenic factors.
Mitra
Biswa Nath
BN
Department of Parasitology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-851, Japan.
Saito-Nakano
Yumiko
Y
Nakada-Tsukui
Kumiko
K
Sato
Dan
D
Nozaki
Tomoyoshi
T
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D020126:Brefeldin A / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology; D004748:Entamoeba histolytica / Q000166:cytology / Q000201:enzymology* / Q000472:pathogenicity; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D013347:Subcellular Fractions / Q000201:enzymology; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
D015415:Biomarkers; D020126:Brefeldin A; D003546:Cysteine Endopeptidases; D007527:Isoenzymes; D015800:Protozoan Proteins; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins