1.C.87 The Channel-forming Vibrio Type III Secretion Effector, VopQ (VopQ) Family
Defects in normal mammalian autophagic pathways are implicated in numerous human diseases such as neurodegenerative diseases, cancer and cardiomyopathy, highlighting the importance of autophagy and its proper regulation. Sreelatha et al. (2013) showed that Vibrio parahaemolyticus uses the type III effector VopQ (Vibrio outer protein Q) to alter autophagic flux by manipulating the partitioning of small molecules and ions in the lysosome. This effector binds to the conserved Vo domain of the vacuolar-type H+-ATPase and causes deacidification of the lysosomes within minutes of entering the host cell. VopQ forms a gated channel ∼18 Å in diameter that facilitates outward flux of ions across lipid bilayers. The electrostatic interactions of this type III secretion system effector with target membranes dictate its preference for host vacuolar-type H+-ATPase-containing membranes, indicating that its pore-forming activity is specific and not promiscuous. As seen with other effectors, VopQ exploites a eukaryotic mechanism, in this case, manipulating lysosomal homeostasis and autophagic flux through transmembrane permeation.