Giardia is a flagellated protozoan parasite that resides in the upper small intestine of several vertebrate hosts, including humans, and is one of the most frequent causes of defined waterborne diarrhea worldwide. Unlike more evolved cells, Giardia lacks of a defined endosomal/lysosomal system, instead it possesses peripheral vacuoles (PVs) with characteristics of endosome and lysosomes, located underneath the plasma membrane. These vacuoles play a central role controlling the endocytosis, degradation, recycling, and secretion of proteins during growth and differentiation of the parasite. The purpose of the present study is to investigate the endocytosis and secretion process of PVs-resident proteins during Giardia growth. We will analyze the role of the molecules involved in protein trafficking from the plasma membrane toward the PVs and characterize novel PVs-resident proteins as well. Because Giardia is an early branching protist, the study of vesicular transport in this parasite will lead to a clearer understanding of the minimal machinery required for protein transport in more evolved cells. Besides, enlighten the endosomal-lysosomal pathway in Giardia may contribute to the design of therapeutic agents against this important human pathogen.

Agency
National Institute of Health (NIH)
Institute
Fogarty International Center (FIC)
Type
Research Project (R01)
Project #
5R01TW007245-05
Application #
8115181
Study Section
Special Emphasis Panel (ZRG1-BDA-K (50))
Program Officer
Liu, Xingzhu
Project Start
2007-08-01
Project End
2012-07-31
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
5
Fiscal Year
2011
Total Cost
$50,252
Indirect Cost
Name
Instituto Invest Medi Mercedes/Ferreyra
Department
Type
DUNS #
971339601
City
Cordoba
State
Country
Argentina
Zip Code
5000
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Miras, Silvana L; Merino, MarĂ­a C; Gottig, Natalia et al. (2013) The giardial VPS35 retromer subunit is necessary for multimeric complex assembly and interaction with the vacuolar protein sorting receptor. Biochim Biophys Acta 1833:2628-2638
Touz, Maria C; Rivero, Maria R; Miras, Silvana L et al. (2012) Lysosomal protein trafficking in Giardia lamblia: common and distinct features. Front Biosci (Elite Ed) 4:1898-909
Rivero, Maria R; Miras, Silvana L; Quiroga, Rodrigo et al. (2011) Giardia lamblia low-density lipoprotein receptor-related protein is involved in selective lipoprotein endocytosis and parasite replication. Mol Microbiol 79:1204-19
Rivero, Maria R; Kulakova, Liudmila; Touz, Maria C (2010) Long double-stranded RNA produces specific gene downregulation in Giardia lamblia. J Parasitol 96:815-9
Rivero, Maria R; Vranych, Cecilia V; Bisbal, Mariano et al. (2010) Adaptor protein 2 regulates receptor-mediated endocytosis and cyst formation in Giardia lamblia. Biochem J 428:33-45