Actin sequestering protein, profilin, regulates intracellular vesicle transport in Leishmania

Ambaru, Bindu; Gopalsamy, Anupriya; Tammana, Trinadh Venkata Satish; Subramanya, Hosahalli; Gupta, Chhitar M

doi:10.1016/j.molbiopara.2020.111280

Cited by 8 publications

(27 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TbAct1 and TbMyo1 are essential for survival of the blood stream form of T. brucei , as knockdown of TbAct1 or TbMyo1 gene by RNAi eventually resulted in cell death ( García-Salcedo et al, 2004 ; Spitznagel et al, 2010 ). Further, despite repeated attempts, homozygous mutants of LdPfn could not be generated ( Ambaru et al, 2020 ), indicating that this protein is perhaps essential for survival of Leishmani a. This is in accordance with the earlier observations that profilin depletion affected the survival of both procyclic and bloodstream forms of T. brucei ( Alsford et al, 2011 ).…”

Section: Discussionsupporting

confidence: 85%

“…In trypanosomatid profilins, LdPfn is the most characterized protein ( Ambaru et al, 2020 ). This protein besides localizing to the cytoplasm, it was also localized to the flagellum, the nucleus and the kinetoplast.…”

Section: Trypanosomatid Actins and Actin Binding Proteinsmentioning

confidence: 99%

“…However, among phosphoinositides, it bound more efficiently to PI (3,5) P2, which is found on early or late endosomes and lysosomes ( Wallroth and Haucke, 2018 ), as compared to PI (4,5) P2 and PI (3,4,5) P3 ( Ambaru et al, 2020 ). Further, LdPfn heterozygous mutants, prepared through targeted replacement of LdPfn gene by selective marker gene, grew at much slower pace, compared to wild type cells, in culture, and displayed slower intracellular trafficking activity ( Ambaru et al, 2020 ). These defects were, however, reversed upon episomal complementation of LdPfn gene, indicating that profilin plays an important role in intracellular trafficking.…”

Section: Trypanosomatid Actins and Actin Binding Proteinsmentioning

confidence: 99%

See 2 more Smart Citations

Emerging Functions of Actins and Actin Binding Proteins in Trypanosomatids

Gupta

Ambaru

Bajaj

2020

Front. Cell Dev. Biol.

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 85%

Section: Trypanosomatid Actins and Actin Binding Proteinsmentioning

confidence: 99%

Section: Trypanosomatid Actins and Actin Binding Proteinsmentioning

confidence: 99%

See 1 more Smart Citation

Emerging Functions of Actins and Actin Binding Proteins in Trypanosomatids

Gupta

Ambaru

Bajaj

2020

Front. Cell Dev. Biol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…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;Tosetti et al, 2019;Dippe, von Dippe, and Levy, 1982;McConville et al, 2002;Stortz et al, 2019). 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). This class of distinguished actin-binding proteins formin plays a curious role in a eukaryotic organism, including a parasite group but it is still not functionally characterized in Leishmania.…”

Section: Discussionmentioning

confidence: 99%

“…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).…”

Section: Discussionmentioning

confidence: 99%

Formins play important role inLeishmaniaphysiology by acting as cytosolic actin bundlers

Kushwaha

Seth

Jijumon

et al. 2021

Preprint

View full text Add to dashboard Cite

Formin proteins regulate actin dynamics, are conserved throughout the eukaryotes cells. They play an important role in cell adhesion, motility, vesicular trafficking, and cytokinesis. Formins from class Kinetoplastida which includes infective organisms such as Leishmania and Trypanosoma not characterized to date, even though they are shown to be important in other protozoan parasites. The protozoan parasite Leishmania major (Lm) has two homologous formin proteins; LmForminA and LmForminB. Our study showed that LmForminA and LmForminB are expressed at RNA and protein levels in L. major cells. LmForminA and LmForminB are localized in the cytosol in patchy distribution patterns. LmForminA and LmForminB puncta also colocalize with the actin patches. The biochemical properties of L. major formins divulge that both formins are potent actin nucleator. LmForminA and LmForminB bind with the actin filament and have actin-bundling activity. We have also observed that formin inhibitor SMIFH2 influences the growth and physiology of L. major cells indicating formins are important for the Leishmania parasite.

show abstract