Kumar Gaurav, Kajuluri Lova P, Gupta Chhitar M, Sahasrabuddhe Amogh A
CSIR-Central Drug Research Institute, Jankipuram Extension-10, Sitapur Road, Lucknow, PIN-226 031, India.
Department of Biosciences, Institute of Bioinformatics and Applied Biotechnology, Biotech Park, Electronics City, Phase-I, Bangaluru, PIN-560 100, India.
Mol Microbiol. 2016 Apr;100(1):173-87. doi: 10.1111/mmi.13310. Epub 2016 Feb 19.
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.
双肌动蛋白结合蛋白是一种在进化上保守的肌动蛋白结合蛋白，它调节真核细胞中的肌动蛋白动力学。在导致人类疾病的各种原生动物寄生虫的基因组中已检测到该蛋白的同源物。然而，对于它们在这些生物体中的核心功能知之甚少。我们在此表明，人类病原体利什曼原虫中的一种双肌动蛋白结合蛋白同源物主要定位于核仁，并且在一定程度上也存在于基体区域。在分裂细胞中，核仁双肌动蛋白结合蛋白重新分布到有丝分裂纺锤体，并部分地与纺锤体微管保持关联。我们进一步表明，由于细胞分裂周期S期进展缓慢，该蛋白约50%的缺失会显著阻碍细胞生长，这是由于核DNA合成延迟所致。有趣的是，该蛋白的过表达导致分裂的利什曼原虫细胞中有丝分裂纺锤体的长度显著增加，而其缺失则对纺锤体伸长和结构产生不利影响。我们的结果表明，双肌动蛋白结合蛋白一方面控制DNA合成，另一方面控制有丝分裂纺锤体伸长，从而有助于利什曼原虫的核分裂。
