Deeply in the Lysosomal protein trafficking of the Primitive Parasite Giardia lamblia

RIVERO MR; VRANYCH CV; ROPOLO AS; TOUZ MC

Chascomus. Buenos Aires.

Simposio; XXII Reunion Cientifica Anual. Sociedad Argentina de Protozoología y Enfermedades Parasitarias 2007; 2007

Sociedad Argentina de Protozoología y Enfermedades Parasitarias

Deeply in the lisosomal protein trafficking of a primitive eukaryotic parasite Giardia lamblia. RIVERO MR, ROPOLO AS, TOUZ MC. Instituto de Investigacion Medica Mercedes y Martin Ferreyra, CONICET. Cordoba. Argentina. rrivero@immf.uncor.edu Unlike yeast and mammalian cells, the lysosomal sorting pathway is not well defined in Giardia. In more evolved cells, soluble hydrolases are sorted from the trans-Golgi network to the endosomal/lysosomal system through a receptor-mediated process. To recruit these proteins, several adaptor proteins (APs) recognize tyrosine-based (YXXÖ) or dileucine-based motifs in the cytoplasmic tail of transmembrane protein. Recently, we found that the delivering of the soluble acid phosphatase (AcPh) to the lysosome-like Peripheral Vacuoles (PVs) is gAP1-dependent. However, the receptor that links AcPh and gAP1 was never described. By performing pull-down and mass-spectrometry assays using H6-tagged AcPh, we found a membrane protein of unknown function with characteristic that full fit for a Giardia hidrolase receptor (gHR). Several protein-protein interactions experiments (YTH and IPP) performed have confirmed the gHR-AcPh interaction. Moreover, IFA shows that gHR possesses a subcellular distribution similar to the AcPh. Our results strongly suggest that gHR acts as a receptor for proper sorting and delivery of AcPh to the PVs. Down-regulation of the gHR expression will be attempted for the well-understanding of its role. We believe that all these studies will provide information about alternative lysosomal-enzyme targeting pathways using by this important parasite. Furthermore, they may also contribute to increase the knowledge for human lysosomal diseases.