Abstract
Motility and phagocytosis are key processes that are involved in invasive amoebiasis disease caused by intestinal parasite Entamoeba histolytica. Previous studies have reported unconventional myosins to play significant role in membrane based motility as well as endocytic processes. EhMyosin IB is the only unconventional myosin present in E. histolytica, is thought to be involved in both of these processes. Here, we report an interaction between the SH3 domain of EhMyosin IB and c-terminal domain of EhFP10, a Rho guanine nucleotide exchange factor. EhFP10 was found to be confined to Entamoeba species only, and to contain a c-terminal domain that binds and bundles actin filaments. EhFP10 was observed to localize in the membrane ruffles, phagocytic and macropinocytic cups of E. histolytica trophozoites. It was also found in early pinosomes but not early phagosomes. A crystal structure of the c-terminal SH3 domain of EhMyosin IB (EhMySH3) in complex with an EhFP10 peptide and co-localization studies established the interaction of EhMySH3 with EhFP10. This interaction was shown to lead to inhibition of actin bundling activity and to thereby regulate actin dynamics during endocytosis. We hypothesize that unique domain architecture of EhFP10 might be compensating the absence of Wasp and related proteins in Entamoeba, which are known partners of myosin SH3 domains in other eukaryotes. Our findings also highlights the role of actin bundling during endocytosis.
Highlights
Entamoeba histolytica is the causative agent of amoebiasis disease in humans, a major public health problem in developing countries
Unconventional myosins are a type of myosin which are different from myosin present in muscles, and are involved in regulation of membrane dependent processes crucial for cellular movement and endocytosis
Even in simple eukaryotes like yeast and amoebazoa, myosin I exists in several isoforms, which carry out distinct functions [8,9,10] but the genome of E. histolytica has a single isoform of myosin I, namely EhMyosin IB [11]
Summary
Entamoeba histolytica is the causative agent of amoebiasis disease in humans, a major public health problem in developing countries. Amoebiasis is the third-leading cause of deaths resulting from parasitic infections [1, 2]. Phagocytosis is associated with intensive cytoskeletal remodeling, which involves actin filaments, several actin-binding proteins, and myosins. Unconventional myosin I constitutes the largest class of the myosin superfamily [5] and has been associated with a variety of membrane-based motility processes such as pinocytosis, membrane ruffling, lamellipodia and filopodia as well as phagocytosis [6, 7], but the detailed mechanisms and pathways of the associations of myosin I with these processes remain to be studied. Even in simple eukaryotes like yeast and amoebazoa, myosin I exists in several isoforms, which carry out distinct functions [8,9,10] but the genome of E. histolytica has a single isoform of myosin I, namely EhMyosin IB [11]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
