biostudies-literatureChavan SDepartment of Biotechnology, Ministry of Science and Technology, India392https://www.ebi.ac.uk/biostudies/studies/S-EPMC11071952biostudies-literatureUnknown79(7)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,Cellular and molecular life sciences : CMLSRanGTPase links nucleo-cytoplasmic transport to the recruitment of cargoes into small extracellular vesicles.PMC11071952BT/PR32331/BRB/10/1774/2019Rapole SJoseph JChavan SLonare ABellare JKhuperkar DSeshadri VPanigrahi SfalseRanGTPase links nucleo-cytoplasmic transport to the recruitment of cargoes into small extracellular vesicles.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,2022-01-01T00:00:00Z2022 Jul2026-06-01T18:48:36.831Z2026-05-19T03:07:08.55ZS-EPMC110719523577917110.1007/s00018-022-04422-y