Secretory granule biogenesis during Giardia lamblia differentiation into cyst

TOUZ, M.C., GOTTIG N., ELIAS V.E., QUIROGA, R., NORES M.J., SOLARI A., LUJÁN H. D.

Marine Biological Laboratory, Woods Hole, Massachusetts, USA.

Congreso; Molecular Parasitology Meeting; 2006

Marine Biological Laboratory

The early branching protist Giardia lamblia is an intestinal parasite that has a simple life cycle alternating between the vegetative trophozoite and the infective cyst. During encystation, cyst wall proteins are specifically expressed and concentrated within encystation-specific secretory vesicles (ESVs), which are typical secretory granules that transport cyst wall proteins (CWPs) before exocytosis and extracellular polymerization. Although CWP1, 2 and 3 are structurally similar in their 26 kDa leucine-rich overlapping region, CWP2 is distinguished by the presence of a 13 kDa carboxy-terminal basic extension. In non-encysting trophozoites, expression of different CWP chimeras indicate that the CWP2 basic extension is necessary for biogenesis of ESVs, which occurs in a compartment derived from the endoplasmic reticulum. Nevertheless, the basic extension of CWP2 by itself is insufficient to trigger ESVs formation, indicating that other domains in CWPs are also required. We found CWP2 is a key regulator of ESVs formation by acting both as an aggregation factor for the other CWPs and as a ligand for sorting, demonstrating that granule formation and maturation requires complex interactions among granule components, membrane receptors, chaperones, and calcium-binding proteins.