Membrane-Associated Proteins in Giardia lamblia

Abstract

The manner in which membrane-associated proteins interact with the membrane defines their subcellular fate and function. This interaction relies on the characteristics of the proteins, their journey after synthesis, and their interaction with other proteins or enzymes. Understanding these properties may help to define the function of a protein and also the role of an organelle. In the case of microorganisms like protozoa parasites, it may help to understand singular features that will eventually lead to the design of parasite-specific drugs. The protozoa parasite Giardia lamblia is an example of a widespread parasite that has been infecting humans and animals from ancestral times, adjusting itself to the changes of the environment inside and outside the host. Several membrane-associated proteins have been posted in the genome database GiardiaDB, although only a few of them have been characterized. This review discusses the data regarding membrane-associated proteins in relationship with lipids and specific organelles and their implication in the discovery of anti-giardial therapies.

Keywords: PX domain; lysosomal vacuoles; palmitoylation; phosphoinositides; variant-specific surface protein.

Figure 1

Variant-specific surface protein or VSP. (A) Confocal immunofluorescence image showing the plasma membrane localization of the VSP9B10 (green) by using FITC-labeled anti-9B10 mAb. The nuclei are stained with DAPI (blue). Scale bars: 5 μm. VSP9B10 covers two of the trophozoites observed. (B) Schematic representation of a VSP containing a signal peptide, an extracellular variable domain, a transmembrane (TM) domain, and the CRGKA invariable cytoplasmic tail. The sites of palmitoylation (underlined C) and citrullination (the asterisk in R) of the cytoplasmic tail are denoted.

Figure 2

Schematic representation of Giardia lamblia proteins localization. Left panel, confocal microscopy merged image showing differential interference contrast, encystation-specific cysteine protease (ESCP)-HA localization in the PVs (green), and the nuclei labelled with DAPI (blue). The right panel shows a draw of proteins that travel from the plasma membrane to the PVs (green arrow), those that use the retromer transport (red arrow), the ones that go from the ER to the PVs (blue arrow), and the integral membrane proteins. Only the proteins with demonstrated experimental localization are denoted. SNXs: sorting nexins.