title: A twinfilin-like protein coordinates karyokinesis by influencing mitotic spindle elongation and DNA replication in Leishmania.
abstract: Twinfilin is an evolutionarily conserved actin-binding protein, which regulates actin-dynamics in eukaryotic cells. Homologs of this protein have been detected in the genome of various protozoan parasites causing diseases in human. However, very little is known about their core functions in these organisms. We show here that a twinfilin homolog in a human pathogen Leishmania, primarily localizes to the nucleolus and, to some extent, also in the basal body region. In the dividing cells, nucleolar twinfilin redistributes to the mitotic spindle and remains there partly associated with the spindle microtubules. We further show that approximately 50% depletion of this protein significantly retards the cell growth due to sluggish progression of S phase of the cell division cycle, owing to the delayed nuclear DNA synthesis. Interestingly, overexpression of this protein results in significantly increased length of the mitotic spindle in the dividing Leishmania cells, whereas, its depletion adversely affects spindle elongation and architecture. Our results indicate that twinfilin controls on one hand, the DNA synthesis and on the other, the mitotic spindle elongation, thus contributing to karyokinesis in Leishmania.
authors.affiliation: CSIR-Central Drug Research Institute, Jankipuram Extension-10, Sitapur Road, Lucknow, PIN-226 031, India.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Kumar
authors.affiliation: CSIR-Central Drug Research Institute, Jankipuram Extension-10, Sitapur Road, Lucknow, PIN-226 031, India.
authors.forename: Lova P
authors.initials: LP
authors.lastname: Kajuluri
authors.affiliation: Department of Biosciences, Institute of Bioinformatics and Applied Biotechnology, Biotech Park, Electronics City, Phase-I, Bangaluru, PIN-560 100, India.
authors.forename: Chhitar M
authors.initials: CM
authors.lastname: Gupta
authors.affiliation: CSIR-Central Drug Research Institute, Jankipuram Extension-10, Sitapur Road, Lucknow, PIN-226 031, India.
authors.forename: Amogh A
authors.initials: AA
authors.lastname: Sahasrabuddhe
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D002455:Cell Division; D002466:Cell Nucleolus / Q000378:metabolism; D048750:Cell Nucleus Division; D004261:DNA Replication; D015870:Gene Expression; D007891:Leishmania / Q000235:genetics* / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D015800:Protozoan Proteins / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: D008840:Microfilament Proteins; D015800:Protozoan Proteins