Donald K. Johnson Eye Institute, Krembil Research Institute, University Health Network, Toronto, ON, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
EMBO J. 2021 Nov 15;40(22):e107264. doi: 10.15252/embj.2020107264. Epub 2021 Sep 8.
Emerging evidence suggests that intracellular molecules and organelles transfer between cells during embryonic development, tissue homeostasis and disease. We and others recently showed that transplanted and host photoreceptors engage in bidirectional transfer of intracellular material in the recipient retina, a process termed material transfer (MT). We used cell transplantation, advanced tissue imaging approaches, genetic and pharmacologic interventions and primary cell culture to characterize and elucidate the mechanism of MT. We show that MT correlates with donor cell persistence and the accumulation of donor-derived proteins, mitochondria and transcripts in acceptor cells in vivo. MT requires cell contact in vitro and is associated with the formation of stable microtubule-containing protrusions, termed photoreceptor nanotubes ( NTs), that connect donor and host cells in vivo and in vitro. NTs mediate GFP transfer between connected cells in vitro. Furthermore, interfering with NT outgrowth by targeting Rho GTPase-dependent actin remodelling inhibits MT in vivo. Collectively, our observations provide evidence for horizontal exchange of intracellular material via nanotube-like connections between neurons in vivo.
新出现的证据表明，细胞内分子和细胞器在胚胎发育、组织稳态和疾病过程中在细胞之间转移。我们和其他人最近表明，在受体内，移植的和宿主的光感受器之间发生细胞内物质的双向转移，这一过程称为物质转移（MT）。我们使用细胞移植、先进的组织成像方法、遗传和药理学干预以及原代细胞培养来表征和阐明 MT 的机制。我们表明，MT 与供体细胞的持久性以及在体内接受细胞中积累的供体来源的蛋白质、线粒体和转录本相关。MT 在体外需要细胞接触，并与形成稳定的含有微管的突起（称为光感受器纳米管（NTs））相关，NTs 在体内和体外连接供体和宿主细胞。NTs 在体外连接的细胞之间介导 GFP 的转移。此外，通过靶向 Rho GTPase 依赖性肌动蛋白重塑来干扰 NT 的生长，可抑制体内的 MT。总的来说，我们的观察结果为神经元之间通过类似纳米管的连接进行细胞内物质的水平交换提供了证据。
