Photoreceptor nanotubes mediate the in vivo exchange of intracellular material

• DOI: 10.15252/embj.2020107264
• Publication Date: 2021-09-08T10:56:53Z
• Authors: Arturo Ortin‐Mart...; Nicole E Yan; En Leh Samuel Tsai; Lacrimioara Comanita; Akshay Gurdita; Nobuhiko Tachibana; Zhongda C Liu; Suying Lu; Parnian Dolati; Neno T Pokrajac; Ahmed El‐Sehemy; Philip E B Nickerson; Carol Schuurmans; Rod Bremner; Valerie A Wallace
• Keywords: Male; rho GTP-Binding Proteins; 0301 basic medicine; Cell Survival; Green Fluorescent Proteins; Retinoblastoma; Biological Transport; Mice, Transgenic; Articles; Actins; Retina; Mitochondria; Mice, Inbred C57BL; Extracellular Vesicles; 03 medical and health sciences; Animals; Humans; Female; Transducin; Photoreceptor Cells, Vertebrate

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 (Ph NTs), that connect donor and host cells in vivo and in vitro. Ph NTs mediate GFP transfer between connected cells in vitro. Furthermore, interfering with Ph 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.