Trans -endocytosis elicited by nectins transfers cytoplasmic cargo, including infectious material, between cells

• Published in: Journal of cell science Vol. 132; no. 16
• Main Authors: Generous, Alex R, Harrison, Oliver J, Troyanovsky, Regina B, Mateo, Mathieu, Navaratnarajah, Chanakha K, Donohue, Ryan C, Pfaller, Christian K, Alekhina, Olga, Sergeeva, Alina P, Indra, Indrajyoti, Thornburg, Theresa, Kochetkova, Irina, Billadeau, Daniel D, Taylor, Matthew P, Troyanovsky, Sergey M, Honig, Barry, Shapiro, Lawrence, Cattaneo, Roberto
• Format: Journal Article
• Language: English
• Published: England Company of Biologists 23.08.2019; The Company of Biologists Ltd
• Subjects: Biological Transport, Active - genetics; Cell Adhesion - genetics; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell Line; Endocytosis; Epithelial Cells - metabolism; Humans; Life Sciences; Measles virus - genetics; Measles virus - metabolism; Microbiology and Parasitology; Nectins - genetics; Nectins - metabolism; Virology; Virus Internalization; Measles virsus; Virus receptor; Nectin; Cell adhesion; Cytoplasm transfer; Cell communication; Trans-endocytosis; Neuronal entry
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.235507

Here, we show that cells expressing the adherens junction protein nectin-1 capture nectin-4-containing membranes from the surface of adjacent cells in a -endocytosis process. We find that internalized nectin-1-nectin-4 complexes follow the endocytic pathway. The nectin-1 cytoplasmic tail controls transfer: its deletion prevents -endocytosis, while its exchange with the nectin-4 tail reverses transfer direction. Nectin-1-expressing cells acquire dye-labeled cytoplasmic proteins synchronously with nectin-4, a process most active during cell adhesion. Some cytoplasmic cargo remains functional after transfer, as demonstrated with encapsidated genomes of measles virus (MeV). This virus uses nectin-4, but not nectin-1, as a receptor. Epithelial cells expressing nectin-4, but not those expressing another MeV receptor in its place, can transfer infection to nectin-1-expressing primary neurons. Thus, this newly discovered process can move cytoplasmic cargo, including infectious material, from epithelial cells to neurons. We name the process nectin-elicited cytoplasm transfer (NECT). NECT-related endocytosis processes may be exploited by pathogens to extend tropism. This article has an associated First Person interview with the first author of the paper.