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

Alex R. Generous, Oliver J. Harrison, Regina B. Troyanovsky, Mathieu Mateo, Chanakha K. Navaratnarajah, Ryan C. Donohue, Christian K. Pfaller, Olga Alekhina, Alina P. Sergeeva, Indrajyoti Indra, Theresa Thornburg, Irina Kochetkova, Daniel D. Billadeau, Matthew P. Taylor, Sergey M. Troyanovsky, Barry Honig, Lawrence Shapiro, Roberto Cattaneo

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


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 trans-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 trans-endocytosis, while its exchange with the nectin-4 tail reverses transfer direction. Nectin-1-expressing cells acquire dyelabeled 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 trans-endocytosis processes may be exploited by pathogens to extend tropism.

Original languageEnglish (US)
Article numberjcs235507
JournalJournal of cell science
Issue number16
StatePublished - Aug 2019


  • Cell adhesion
  • Cell communication
  • Cytoplasm transfer
  • Measles virsus
  • Nectin
  • Neuronal entry
  • Transendocytosis
  • Virus receptor

ASJC Scopus subject areas

  • Cell Biology


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