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基于成像的筛选鉴定出了扰乱细胞和叶绿体分裂的新型天然化合物。

Imaging-based screen identifies novel natural compounds that perturb cell and chloroplast division in .

作者信息

Clark-Cotton Manuella R, Chen Sheng-An, Gomez Aracely, Mulabagal Aditya J, Perry Adriana, Malhotra Varenyam, Onishi Masayuki

机构信息

Department of Biology, Duke University, Durham, NC 27708.

Project SEED, North Carolina Section, American Chemical Society, Chapel Hill, NC 27514.

出版信息

Mol Biol Cell. 2025 Apr 1;36(4):br14. doi: 10.1091/mbc.E24-09-0425. Epub 2025 Feb 28.

Abstract

Successful cell division requires faithful division and segregation of organelles into daughter cells. The unicellular alga has a single, large chloroplast whose division is spatiotemporally coordinated with furrowing. Cytoskeletal structures form in the same plane at the midzone of the dividing chloroplast (FtsZ) and the cell (microtubules), but how these structures are coordinated is not understood. Previous work showed that loss of F-actin blocks chloroplast division but not furrow ingression, suggesting that pharmacological perturbations can disorganize these events. In this study, we developed an imaging platform to screen natural compounds that perturb cell division while monitoring FtsZ and microtubules and identified 70 unique compounds. One compound, curcumin, has been proposed to bind to both FtsZ and tubulin proteins in bacteria and eukaryotes, respectively. In where both targets coexist and are involved in cell division, curcumin at a specific dose range caused a severe disruption of the FtsZ ring in chloroplast while leaving the furrow-associated microtubule structures largely intact. Time-lapse imaging showed that loss of FtsZ and chloroplast division failure delayed the completion of furrowing but not the initiation, suggesting that the chloroplast division checkpoint proposed in other algae requires FtsZ or is absent altogether in

摘要

成功的细胞分裂需要将细胞器准确地分裂并分配到子细胞中。单细胞藻类有一个单一的大型叶绿体,其分裂在时空上与细胞缢缩协调进行。细胞骨架结构在分裂叶绿体的中区(FtsZ)和细胞(微管)的同一平面上形成,但这些结构是如何协调的尚不清楚。先前的研究表明,F-肌动蛋白的缺失会阻断叶绿体分裂,但不会影响细胞缢缩的进行,这表明药物干扰会打乱这些事件。在本研究中,我们开发了一个成像平台,用于筛选在监测FtsZ和微管的同时干扰细胞分裂的天然化合物,并鉴定出70种独特的化合物。一种化合物姜黄素,已被提出分别在细菌和真核生物中与FtsZ和微管蛋白结合。在两个靶点共存且都参与细胞分裂的情况下,特定剂量范围内的姜黄素会导致叶绿体中FtsZ环严重破坏,而与细胞缢缩相关的微管结构基本保持完整。延时成像显示,FtsZ的缺失和叶绿体分裂失败会延迟细胞缢缩的完成,但不会延迟其起始,这表明其他藻类中提出的叶绿体分裂检查点需要FtsZ,或者在......中完全不存在。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12cf/12005104/2fa95e6754c0/mbc-36-br14-g001.jpg

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