Glutamic acid-lysine (EK) rich motif of RabD2 self-associates and regulates adhesion through multivesicular bodies in Entamoeba histolytica.

backgroundEntamoeba histolytica, an enteric pathogen, causes disease by adhering to and destroying the host tissues. The interaction between the parasite and host tissue enables the rewiring of gene expression and global membrane trafficking in the parasite. A fine balance between endocytosis and exocytosis of cargoes/receptors is required to establish infection in the host. Multivesicular bodies (MVBs) act as sorting platforms, delivering cargoes/receptors to lysosomes for degradation or secreting their contents through plasma membrane fusion. Some small GTPases are known to control MVB biogenesis in various organisms. However, the functional contribution of Rab GTPases in MVB biogenesis is poorly studied in E. histolytica.

resultsHere, we identified a novel atypical protein RabD2, with an N-terminal glutamic acid-lysine rich motif and a C-terminal conserved Rab domain. Our biochemical and cell biological assays provide evidence that RabD2 self-associates, and this interaction is controlled by the N-terminal EK-rich motif and the GTPase activity mutants. RabD2 localizes on the surface of MVBs and controls their biogenesis. In line with these findings, overexpression of RabD2 upregulates ubiquitination levels, directing the decreased abundance of the heavy chain of GalNAc lectin, ultimately leading to decreased adherence of E. histolytica trophozoites to host cells.

conclusionsThus, amoebic RabD2 is a new class of Rab protein that forms high-ordered self-association variants and controls adhesion to the host cells, which impacts the pathogenesis of E. histolytica through the biogenesis of MVBs.