RanGTPase links nucleo-cytoplasmic transport to the recruitment of cargoes into small extracellular vesicles

Cell Mol Life Sci. 2022 Jul 2;79(7):392. doi: 10.1007/s00018-022-04422-y.


Small extracellular vesicle (sEV)-mediated intercellular communication regulates multiple aspects of growth and development in multicellular organisms. However, the mechanism underlying cargo recruitment into sEVs is currently unclear. We show that the key nucleo-cytoplasmic transport (NCT) protein-RanGTPase, in its GTP-bound form (RanGTP), is enriched in sEVs secreted by mammalian cells. This recruitment of RanGTP into sEVs depends on the export receptor CRM1 (also called XPO1). The recruitment of GAPDH, a candidate cargo protein, into sEVs is regulated by the RanGTP-CRM1axis in a nuclear export signal (NES)-dependent manner. Perturbation of NCT through overexpression or depletion of nuclear transport components affected the recruitment of Ran, CRM1 and GAPDH into sEVs. Our studies, thus, suggest a link between NCT, particularly the Ran-CRM1 axis, and recruitment of NES-containing cargoes into the sEVs. Collectively, these findings implicate RanGTPase as a link between NCT and sEV mediated intercellular communication.

Keywords: Exosome; Exportin1/CRM1; Intercellular communication; Nuclear export signal; RanGTPase; Small extracellular vesicles.

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Cell Communication*
  • Extracellular Vesicles*
  • Mammals
  • Nuclear Export Signals


  • Nuclear Export Signals