Two StAR-related lipid transfer proteins play specific roles in endocytosis, exocytosis, and motility in the parasitic protist Entamoeba histolytica

Abstract

Lipid transfer proteins (LTPs) are the key contributor of organelle-specific lipid distribution and cellular lipid homeostasis. Here, we report a novel implication of LTPs in phagocytosis, trogocytosis, pinocytosis, biosynthetic secretion, recycling of pinosomes, and motility of the parasitic protist E. histolytica, the etiological agent of human amoebiasis. We show that two StAR-related lipid transfer (START) domain-containing LTPs (named as EhLTP1 and 3) are involved in these biological pathways in an LTP-specific manner. Our findings provide novel implications of LTPs, which are relevant to the elucidation of pathophysiology of the diseases caused by parasitic protists.

PTEN differentially regulates endocytosis, migration, and proliferation in the enteric protozoan parasite Entamoeba histolytica

“…As stated above, transferrin, when present at high concentrations, is internalized by receptor independent fashion in E. histolytica [47]. Thus, it is consistent with our observation that E. histolytica internalization of the fluid-phase marker and transferrin by actin-dependent macropinocytosis (S7 and S8 Movies), also as previously shown [52]. We also previously showed that EhAGCK2, which preferentially binds PtdIns(3,4,5)P 3 over PtdIns(4,5)P 2 , is involved in pinocytosis of the fluidphase marker [21], supporting the actin-dependence of macropinocytosis.…”

Entamoeba histolytica EHD1 Is Involved in Mitosome-Endosome Contact

“…Lipid transport and/or metabolism are roles commonly ascribed to MCSs. Although we did not detect any lipid transport proteins in our immunoprecipitation assay, two lipid transport proteins (LTP1 and LTP3) in E. histolytica have been characterized ( 46 ), and it is plausible that various LTPs may transiently interact with amoebic MCSs to facilitate lipid mobility across organelles. We detected a few fatty acid ligases in the ∼90- and ∼180-kDa complexes; however, the interaction of these proteins to the HA-ETMP1-containing complex needs to be experimentally validated.…”

The mitosome of the anaerobic parasitic protist Entamoeba histolytica: A peculiar and minimalist mitochondrion‐related organelle

“…Characterization of two E . histolytica LTPs (LTP1 and LTP3), which belong to the steroidogenic acute regulatory protein‐related lipid‐transfer (START)‐domain‐containing LTPs, were reported (Das et al ., 2021), and similar to other eukaryotes, it is likely that such LTPs are involved in various amoebic organelle MCSs for the purpose of lipid exchange and membrane homeostasis (Santos et al ., 2022). A rigorous lipidomic and proteomic profiling of organellar membranes will further shed light on the mechanisms of lipid transfer in E .…”

“…Although the Entamoeba genome is devoid of homologs for the establishment of the ERMES complex, we suppose that dual-localized membrane proteins point to the potential existence of similar tethering complexes between the ER and mitosomes. Characterization of two E. histolytica LTPs (LTP1 and LTP3), which belong to the steroidogenic acute regulatory protein-related lipidtransfer (START)-domain-containing LTPs, were reported (Das et al, 2021), and similar to other eukaryotes, it is likely that such LTPs are involved in various amoebic organelle MCSs for the purpose of lipid exchange and membrane homeostasis (Santos et al, 2022). A rigorous lipidomic and proteomic profiling of organellar membranes will further shed light on the mechanisms of lipid transfer in E. histolytica.…”