Emerging Functions of Actins and Actin Binding Proteins in Trypanosomatids

Abstract

Actin is the major protein constituent of the cytoskeleton that performs wide range of cellular functions. It exists in monomeric and filamentous forms, dynamics of which is regulated by a large repertoire of actin binding proteins. However, not much was known about existence of these proteins in trypanosomatids, till the genome sequence data of three important organisms of this class, viz. Trypanosoma brucei , Trypanosoma cruzi and Leishmania major , became available. Here, we have reviewed most of the findings reported to date on the intracellular distribution, structure and functions of these proteins and based on them, we have hypothesized some of their functions. The major findings are as follows: (1) All the three organisms encode at least a set of ten actin binding proteins (profilin, twinfilin, ADF/cofilin, CAP/srv2, CAPz, coronin, two myosins, two formins) and one isoform of actin, except that T. cruzi encodes for three formins and several myosins along with four actins. (2) Actin 1 and a few actin binding proteins (ADF/cofilin, profilin, twinfilin, coronin and myosin13 in L. donovani ; ADF/cofilin, profilin and myosin1 in T. brucei ; profilin and myosin-F in T.cruzi ) have been identified and characterized. (3) In all the three organisms, actin cytoskeleton has been shown to regulate endocytosis and intracellular trafficking. (4) Leishmania actin1 has been the most characterized protein among trypanosomatid actins. (5) This protein is localized to the cytoplasm as well as in the flagellum, nucleus and kinetoplast, and in vitro , it binds to DNA and displays scDNA relaxing and kDNA nicking activities. (6) The pure protein prefers to form bundles instead of thin filaments, and does not bind DNase1 or phalloidin. (7) Myosin13, myosin1 and myosin-F regulate endocytosis and intracellular trafficking, respectively, in Leishmania , T. brucei and T. cruzi . (8) Actin-dependent myosin13 motor is involved in dynamics and assembly of Leishmania flagellum. (9) Leishmania twinfilin localizes mostly to the nucleolus and coordinates karyokinesis by effecting splindle elongation and DNA synthesis. (10) Leishmania coronin binds and promotes actin filament formation and exists in tetrameric form rather than trimeric form, like other coronins. (11) Trypanosomatid profilins are essential for survival of all the three parasites.

Cdc42/Rac Interactive Binding Containing Effector Proteins in Unicellular Protozoans With Reference to Human Host: Locks of the Rho Signaling

“…Trypanosoma cruzi causes an encumbering severe illness in humans, known as the Chagas disease, which affects millions of people globally ( de Souza et al, 2010 ). The various species of Trypanosoma belongs to kinetoplastid protozoans in an evolutionary context ( Gupta et al, 2020 ). The complex life cycle involves four developmental stages: 1) epimastigotes; 2) metacyclic trypomastigotes; 3) amastigotes; and 4) bloodstream trypomastigotes ( Zuma et al, 2021 ).…”

“…Highly infective strain’s amastigotes secrete a differentially glycosylated Ssp4 that recruits Galectin-3 (Gal3) to mediate host cell surface and parasite interaction ( Florentino et al, 2018 ). Recent studies on actin-binding proteins from kinetoplastids, proposed a protein (Q4DEX0) as coronin because it has homologous WD repeat and coronin domains characteristic to amoebozoa and higher eukaryotes ( Gupta et al, 2020 ).…”

Formins play important role inLeishmaniaphysiology by acting as cytosolic actin bundlers

“…Recently, formins from parasitic protozoans such as Plasmodium, Toxoplasma have been shown to be very important for infectivity (Baum et al, 2008; Daher et al, 2010; Daher et al, 2012; McConville et al, 2002; Stortz et al, 2019; Tosetti et al, 2019; Von Dippe and Levy, 1982). Nevertheless, nothing was reported in the case of the Kinetoplasts Leishmania, although the importance of actin and other actin-binding proteins such as Arp2/3 complex, cofilin, profilin are well reported (Ambaru et al, 2020; Tammana et al, 2010, Gupta et al, 2020).…”

“…Some actin-binding proteins such as profilin, Arp2/3 protein, cofilin, and coronin are reported in Leishmania , which are involved in different cellular functions from cell division to vesicular trafficking, indicating the importance of actin in the physiology of Leishmania (Nayak et al, 2005; Tammana et al, 2010). However, the functional role of Leishmania formins, an important class of actin-nucleating protein, remains elusive till date (Gupta et al, 2020).…”

To the Surface and Back: Exo- and Endocytic Pathways in Trypanosoma brucei

“…The cytoskeleton is another important factor in endocytosis. Recently, genetic screening confirmed the presence of actin and actin-related proteins in T. brucei (reviewed in Gupta et al, 2020). In bloodstream forms, actin is localized in the posterior region of the cell body, between the nucleus and kinetoplast, and its depletion causes impairment of endocytosis and enlargement of the FP (Garcia-Salcedo et al, 2004).…”