A core UPS molecular complement implicates unique endocytic compartments at the parasite-host interface in Giardia...

Area of Science:

• Cell Biology
• Parasitology
• Molecular Biology

Background:

• Unconventional protein secretion (UPS) is crucial for cell function, bypassing traditional ER/Golgi pathways.
• Giardia lamblia, a parasite, releases virulence factors via UPS without canonical signals, but its machinery remains unknown.
• Speculation exists regarding the role of endocytic organelles, phagosome and endosome-associated compartments (PV/PECs), in Giardia UPS.

Purpose of the Study:

• To investigate if PV/PECs are involved in virulence-associated UPS in Giardia lamblia.
• To identify the molecular machinery responsible for protein release via UPS in this parasite.

Main Methods:

• Affinity purification and mass spectrometry were used to analyze the interactomes of 11 unconventionally secreted proteins.
• Microscopy-based subcellular localization and signal correlation quantification were employed.
• Proteins were predicted to be cytosolic and their association with PV/PECs was assessed.

Main Results:

• A core PV/PECs-associated UPS machinery was identified, including novel coiled-coil proteins and NEK kinases.
• A subset of alpha-giardin proteins was consistently enriched in PV/PECs-associated interactomes.
• The study found that some unconventionally secreted proteins are indeed associated with PV/PECs.

Conclusions:

• This study provides the first characterization of a virulence-associated UPS protein complex in Giardia lamblia.
• The findings suggest a novel link between PV/PECs and UPS at the parasite-host interface.
• Alpha-giardins play a previously unrecognized role in PV/PECs and UPS in Giardia.