QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 15, Issue 7, 3053-3060, July 2004

This Article Full Text Full Text (PDF) All Versions of this Article: E03-10-0744v1 15/7/3053    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Touz, M. C. Articles by Nash, T. E. Search for Related Content PubMed PubMed Citation Articles by Touz, M. C. Articles by Nash, T. E.

Adaptor Protein Complex 1 Mediates the Transport of Lysosomal Proteins from a Golgi-like Organelle to Peripheral Vacuoles in the Primitive Eukaryote Giardia lamblia

Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892

Submitted October 17, 2003; Revised March 11, 2004; Accepted April 12, 2004
Monitoring Editor: Jennifer Lippincott-Schwartz

Giardia lamblia is an early branching protist that possesses peripheral vacuoles (PVs) with characteristics of lysosome-like organelles, located underneath the plasma membrane. In more evolved cells, lysosomal protein trafficking is achieved by cargo recognition involving adaptor protein (AP) complexes that recognize specific amino acid sequences (tyrosine and/or dileucine motifs) within the cytoplasmic tail of membrane proteins. Previously, we reported that Giardia has a tyrosine-based sorting system, which mediates the targeting of a membrane-associated cysteine protease (encystation-specific cysteine protease, ESCP) to the PVs. Here, we show that Giardia AP1 mediates the transport of ESCP and the soluble acid phosphatase (AcPh) to the PVs. By using the yeast two-hybrid assay we found that the ESCP tyrosine-based motif interacts specifically with the medium subunit of AP1 (Giµa). Hemagglutinin-tagged Giµa colocalizes with ESCP and AcPh and coimmunoprecipitates with clathrin, suggesting that protein trafficking toward the PVs is clathrin-adaptin dependent. Targeted disruption of Giµa results in mislocalization of ESCP and AcPh but not of variant-specific surface proteins. Our results suggest that, unlike mammalian cells, only AP1 is involved in anterograde protein trafficking to the PVs in Giardia. Moreover, even though Giardia trophozoites lack a morphologically discernible Golgi apparatus, the presence of a clathrin-adaptor system suggests that this parasite possess a primitive secretory organelle capable of sorting proteins similar to that of more evolved cells.

Abbreviations used: AcPh, acid phosphatase; CCV, clathrin-coated vesicle; CWP2, cyst wall protein 2; ESCP, encystation-specific cysteine protease; GGD, Giardia Genome Database; gDPP, Giardia dipeptidilpeptidase; PV, peripheral vacuole; TGN, trans-Golgi network; VSP, variant-specific surface protein; YXX, tyrosine-based motif.

^* Corresponding author. E-mail address: mtouz{at}niaid.nih.gov.

This article has been cited by other articles:

				M. C. Touz, A. S. Ropolo, M. R. Rivero, C. V. Vranych, J. T. Conrad, S. G. Svard, and T. E. Nash Arginine deiminase has multiple regulatory roles in the biology of Giardia lamblia J. Cell Sci., September 1, 2008; 121(17): 2930 - 2938. [Abstract] [Full Text] [PDF]

				J. E. Vince, D. L. Tull, T. Spurck, M. C. Derby, G. I. McFadden, P. A. Gleeson, S. Gokool, and M. J. McConville Leishmania Adaptor Protein-1 Subunits Are Required for Normal Lysosome Traffic, Flagellum Biogenesis, Lipid Homeostasis, and Adaptation to Temperatures Encountered in the Mammalian Host Eukaryot. Cell, August 1, 2008; 7(8): 1256 - 1267. [Abstract] [Full Text] [PDF]

				H. P. Price, M. Stark, and D. F. Smith Trypanosoma brucei ARF1 Plays a Central Role in Endocytosis and Golgi-Lysosome Trafficking Mol. Biol. Cell, March 1, 2007; 18(3): 864 - 873. [Abstract] [Full Text] [PDF]

				A. Galkin, L. Kulakova, E. Melamud, L. Li, C. Wu, P. Mariano, D. Dunaway-Mariano, T. E. Nash, and O. Herzberg Characterization, Kinetics, and Crystal Structures of Fructose-1,6-bisphosphate Aldolase from the Human Parasite, Giardia lamblia J. Biol. Chem., February 16, 2007; 282(7): 4859 - 4867. [Abstract] [Full Text] [PDF]