Optical Control of the Actin Cytoskeleton

项目摘要/摘要 本项目的目标是利用光开关对肌动蛋白细胞骨架进行光学控制。 分子。这些化合物针对单体G-肌动蛋白、聚合F-肌动蛋白、核因子 我们针对F-肌动蛋白和G-肌动蛋白的探针是 从天然产物茉莉酸激动素衍生而来，产生光学茉莉素，细胞松弛素D(光学-Chal)， 和Latrunculin B(opto-Lat)。Arp2/3的光开关分子来源于 CK-666(Opto-CK)和来自Blebbistatin及类似物的可光切换肌球蛋白2抑制剂 化合物(光-MI)。我们已经在多个方面取得了重大的初步成果 细胞(如酵母、HeLa、神经元、少突胶质细胞、小胶质细胞)。我们提议的计划包括 我们长期和成功的肌动蛋白光学控制计划的继续 微管蛋白，以及与光开关小分子相关的马达蛋白。收盘 化学生物学家和结构生物学家之间的合作将产生有用的探测器 与社区共享，并可能形成新形式的精确度的基础 化疗药物。

Project Summary/Abstract The goal of this project is the optical control of the actin cytoskeleton with photoswitchable molecules. These compounds target monomeric G-actin, polymeric F-actin, the nucleator complex Arp2/3, and the motor protein myosin II. Our probes aimed at F-actin and G-actin are derived from the natural products jasplakinolide, yielding opto-Jasp, cytochalasin D (opto-Chal), and latrunculin B (opto-Lat), respectively. The photoswitchable molecules for Arp2/3 stem from CK-666 (opto-CK) and the photoswitchable myosin 2 inhibitors from blebbistatin and similar compounds (opto-MI). We have already obtained significant preliminary results in a variety of cells (e.g. yeast, HeLa, neurons, oligodendrocytes, microglia). Our proposed program constitutes the continuation of our long-standing and successful program on optically controlling actin and tubulin, as well as associated motor proteins with photoswitchable small molecules. The close collaboration between a chemical biologist and a structural biologist will yield useful probes that are shared with the community and could form the basis of a new form of precision chemotherapeutics.