Tunneling nanotubes (TNTs) are F-actin-based, membrane-enclosed tubular connections between animal cells that transport a variety of cellular cargo. Over the last 15 years since their discovery, TNTs have come to be recognized as key players in normal cell communication and organism development, and are also exploited for the spread of various microbial pathogens and major diseases like cancer and neurodegenerative disorders. TNTs have also been proposed as modalities for disseminating therapeutic drugs between cells. Despite the rapidly expanding and wide-ranging relevance of these structures in both health and disease, there is a glaring dearth of molecular mechanistic knowledge regarding the formation and function of these important but enigmatic structures. A series of fundamental steps are essential for the formation of functional nanotubes. The spatiotemporally controlled and directed modulation of cortical actin dynamics would be required to ensure outward F-actin polymerization. Local plasma membrane deformation to impart negative curvature and membrane addition at a rate commensurate with F-actin polymerization would enable outward TNT elongation. Extrinsic tactic cues, along with cognate intrinsic signaling, would be required to guide and stabilize the elongating TNT towards its intended target, followed by membrane fusion to create a functional TNT. Selected cargoes must be transported between connected cells through the action of molecular motors, before the TNT is retracted or destroyed. This review summarizes the current understanding of the molecular mechanisms regulating these steps, also highlighting areas that deserve future attention.

中文翻译：

---

隧道纳米管和相关结构：形成和功能的分子机制

隧道纳米管 (TNT) 是基于 F-肌动蛋白的、膜封闭的管状连接，在动物细胞之间运输各种细胞货物。自发现以来的过去 15 年中，TNT 已被公认为正常细胞通讯和生物体发育的关键参与者，并且还被用于传播各种微生物病原体和癌症和神经退行性疾病等重大疾病。TNTs 也被提议作为在细胞之间传播治疗药物的方式。尽管这些结构在健康和疾病中的相关性迅速扩大和广泛，但关于这些重要但神秘的结构的形成和功能的分子机制知识明显缺乏。一系列基本步骤对于功能性纳米管的形成至关重要。需要对皮质肌动蛋白动力学进行时空控制和定向调节，以确保向外的 F-肌动蛋白聚合。局部质膜变形以与 F-肌动蛋白聚合相称的速率赋予负曲率和膜添加，将使 TNT 向外伸长。需要外在策略提示以及同源的内在信号传导来引导和稳定拉长的 TNT 朝向其预定目标，然后进行膜融合以创建功能性 TNT。在 TNT 被收回或摧毁之前，选定的货物必须通过分子马达的作用在连接的单元之间运输。这篇综述总结了目前对调节这些步骤的分子机制的理解，同时强调了未来值得关注的领域。