Going ‘off-road’, the molecular mechanism of vesicle originated actin/myosin transport

囊泡起源的肌动蛋白/肌球蛋白运输的分子机制走向“越野”

• 批准号: 462333405
• 负责人: Professor Dr. Eugen Kerkhoff
• 金额: --
• 依托单位: Labor Molekulare Zellbiology (Kerkhoff Lab)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/462333405?language=en
• 关键词: Going; off; road; molecular; mechanism

In our aim to explore the function of actin/myosin force generation in vesicle transport processes, we have discovered a novel transport mechanism in mouse oocytes and melanocytes, which is based on a vesicle originated actin/myosin network. Important factors driving the transport have been identified and include vesicle associated RAB GTPases, class 5 myosin motor proteins, the SPIRE/formin actin nucleator complex and the melanophilin myosin/actin filament/microtubule binding protein. Major questions concerning the mode and order of action of the different factors and the actual force generation mechanism are not yet understood. Our model would suggest that SPIRE/formin cooperation generates actin filaments and that a vesicle interacts in parallel with two actin filaments, in an anchoring and in a processive filament sliding mode. By employing immortalised melanocytes and melanosome transport as a cell culture model system, in combination with in vitro reconstitution of actin/myosin driven motility of microspheres and mathematical modelling, we here propose to study the mechanistic principles of the vesicle originated actin/myosin transport. Our study will contribute to the cell biological understanding of exocytic vesicle transport processes, which determine the polarisation and communication of animal cells.

为了探索肌动蛋白/肌球蛋白力产生在囊泡运输过程中的功能，我们在小鼠卵母细胞和黑素细胞中发现了一种新的运输机制，该机制基于囊泡起源的肌动蛋白/肌球蛋白网络。驱动转运的重要因素已被鉴定，包括囊泡相关RAB GTP酶、5类肌球蛋白马达蛋白、SPIRE/肌动蛋白核因子复合物和亲黑素肌球蛋白/肌动蛋白丝/微管结合蛋白。关于不同因素的作用方式和顺序以及实际的部队产生机制的主要问题尚未得到理解。我们的模型将表明，SPIRE/SPIRE合作产生肌动蛋白丝和囊泡相互作用，平行于两个肌动蛋白丝，在锚定和进行性丝滑动模式。通过采用永生化的黑素细胞和黑素体运输作为细胞培养模型系统，结合肌动蛋白/肌球蛋白驱动的微球运动的体外重建和数学建模，我们在这里建议研究囊泡起源的肌动蛋白/肌球蛋白运输的机械原理。我们的研究将有助于细胞生物学的理解胞吐囊泡运输过程，这决定了动物细胞的极化和通信。