VAMP3 vesicles support host protein recruitment and Plasmodium liver stage development

Chirgwin M.E.; Gan C.; Godinez-Macias K.P.; Choe K.; Shiau J.C.; Calla J.; Kyle D.E.; Winzeler E.A.; Derbyshire E.R. · mBio (2026) · DOI: 10.1128/mbio.01430-26

Resumen

Plasmodium remodels the host liver cell as an obligatory step in malaria infection. Although several host proteins are recruited to the parasitophorous vacuole membrane (PVM) after invasion, the mechanisms underlying this acquisition remain unknown. Here, we validated the upregulation and recruitment of the host protein CGA during liver stage Plasmodium berghei infection. We then depleted a panel of host trafficking proteins to investigate their role in CGA recruitment to the P. berghei PVM. This highlighted the significance of protein exocytosis for host protein acquisition and identified vesicle-associated membrane protein 3 (VAMP3), a SNARE family protein, as critical for CGA recruitment and parasite growth. A phenotypic study revealed that VAMP3 depletion decreased P. berghei survival after invasion, which correlated with enhanced LC3 recruitment. VAMP3 recruitment to the PVM was observed in the rodent-infective P. berghei and the human-infective Plasmodium falciparum, suggesting host vesicle redirection may be a conserved mechanism during the parasite’s liver stage. Expansion microscopy revealed VAMP3 vesicles near and overlapping with the PVM, suggesting fusion events might occur. This proposal was tested using the chemical probe N-ethylmaleimide (NEM), which prevents SNARE recycling. VAMP3 accumulates on the PVM after NEM treatment, consistent with host vesicle fusion to the PVM. Overall, we uncover factors that facilitate Plasmodium’s acquisition of host proteins and provide evidence that the PVM undergoes fusion with host SNARE machinery.

Instituciones: Universidad Nacional Mayor de San Marcos