Structural and Biological Analysis of Retromer Complex in the protozoan parasite Giardia lamblia

MIRAS SL; RIVERO MR; ROPOLO A; TOUZ MC

Montevideo

Conferencia; International Society for Computational Biology Regional Latin American; 2010

ISCB

Giardia lamblia is an early branching microorganism that passes through two stages in their biological life cycle: the trophozoite, a vegetative replication of the parasite, and the cyst, the infective form. This parasite possesses organelles characteristic of eukaryotic organisms like two nuclei, an endoplasmic reticulum (ER), and peripheral vacuoles (PVs) with hydrolytic activity that function simultaneously as endosomes and lysosomes. Although without a typical Golgi apparatus, the transport, distribution, and protein secretion occur normally in Giardia. Early reports showed that there is a specific protein trafficking toward the PVs. In this work, we seek to analyze whether a retromer complex, that mediates the retrograde transport of transmembrane proteins from endosomes to the trans-Golgi network (TGN), exists in this parasite. The retromer is a multimeric complex associated with the cytosolic face of endosomes and is constituted by the protein subcomplex Vps (Vacuolar protein sorting) and the subcomplex proteins belonging to the family of Sorting nexin (SNX) [1]. This has a central role in the transport of transmembrane receptors via a tubulovesicular structure[2]. By searching the GiardiaDB, we found genes that codified to the subcomplex gVps35, gVps29, and gVps26 but not SNX1 or SNX2. Analysis of the sequence and structure of these proteins showed similarities with the ones described in yeast and mammalian cells. We identified specific motifs with central roles in protein function and also predicted the structure of the three Vps subunits of Giardia lamblia. The results of the present work suggest a conserved role of the retromer in the trafficking of lysosomal proteins during development and differentiation. Our results are the first step in the understanding of the biological function of these protein complex in this important parasite. We identified specific motifs with central roles in protein function and also predicted the structure of the three Vps subunits of Giardia lamblia. The results of the present work suggest a conserved role of the retromer in the trafficking of lysosomal proteins during development and differentiation. Our results are the first step in the understanding of the biological function of these protein complex in this important parasite.