A retromerlike complex is a novel Rab7 effector that is involved in the transport of the virulence factor cysteine protease in the enteric protozoan parasite Entamoeba histolytica.
Vesicular trafficking plays an important role in a virulence mechanism of the enteric protozoan parasite Entamoeba histolytica as secreted and lysosomal cysteine protease (CP) contributes to both cytolysis of tissues and degradation of internalized host cells. Despite the primary importance of intracellular sorting in pathogenesis, the molecular mechanism of CP trafficking remains largely unknown. In this report we demonstrate that transport of CP is regulated through a specific interaction of Rab7A small GTPase (EhRab7A) with the retromerlike complex. The amoebic retromerlike complex composed of Vps26, Vps29, and Vps35 was identified as EhRab7A-binding proteins. The amoebic retromerlike complex specifically bound to GTP-EhRab7A, but not GDP-EhRab7A through the direct binding via the carboxy terminus of EhVps26. In erythrophagocytosis the retromerlike complex was recruited to prephagosomal vacuoles, the unique preparatory vacuole of digestive enzymes, and later to phagosomes. This dynamism was indistinguishable from that of EhRab7A, and consistent with the premise that the retromerlike complex is involved in the retrograde transport of putative hydrolase receptor(s) from preparatory vacuoles and phagosomes to the Golgi apparatus. EhRab7A overexpression caused enlargement of lysosomes and decrease of the cellular CP activity. The reduced CP activity was restored by the coexpression of EhVps26, implying that the EhRab7A-mediated transport of CP to phagosomes is regulated by the retromerlike complex.
Nakada-Tsukui
Kumiko
K
Department of Parasitology, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
Saito-Nakano
Yumiko
Y
Ali
Vahab
V
Nozaki
Tomoyoshi
T
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D003546:Cysteine Endopeptidases; D004748:Entamoeba histolytica / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000032:analysis* / Q000187:drug effects / Q000378:metabolism*; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D015800:Protozoan Proteins / Q000032:analysis* / Q000187:drug effects / Q000378:metabolism*; D014617:Vacuoles / Q000378:metabolism; D037521:Virulence Factors; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins
D002352:Carrier Proteins; D046912:Multiprotein Complexes; D015800:Protozoan Proteins; D037521:Virulence Factors; D000090802:rab7 GTP-Binding Proteins; D003546:Cysteine Endopeptidases; D020558:GTP Phosphohydrolases; C464925:Rab7 protein, Entamoeba histolytica; D020691:rab GTP-Binding Proteins