title: Inter-cellular transport of ran GTPase.
abstract: Ran, a member of the Ras-GTPase superfamily, has a well-established role in regulating the transport of macromolecules across the nuclear envelope (NE). Ran has also been implicated in mitosis, cell cycle progression, and NE formation. Over-expression of Ran is associated with various cancers, although the molecular mechanism underlying this phenomenon is unclear. Serendipitously, we found that Ran possesses the ability to move from cell-to-cell when transiently expressed in mammalian cells. Moreover, we show that the inter-cellular transport of Ran is GTP-dependent. Importantly, Ran displays a similar distribution pattern in the recipient cells as that in the donor cell and co-localizes with the Ran binding protein Nup358 (also called RanBP2). Interestingly, leptomycin B, an inhibitor of CRM1-mediated export, or siRNA mediated depletion of CRM1, significantly impaired the inter-cellular transport of Ran, suggesting a function for CRM1 in this process. These novel findings indicate a possible role for Ran beyond nucleo-cytoplasmic transport, with potential implications in inter-cellular communication and cancers.
authors.affiliation: National Centre for Cell Science, Ganeshkhind, Pune, India.
authors.forename: Deepak
authors.initials: D
authors.lastname: Khuperkar
authors.affiliation: National Centre for Cell Science, Ganeshkhind, Pune, India.
authors.forename: Mary
authors.initials: M
authors.lastname: Helen
authors.affiliation: National Centre for Cell Science, Ganeshkhind, Pune, India.
authors.forename: Indrasen
authors.initials: I
authors.lastname: Magre
authors.affiliation: National Centre for Cell Science, Ganeshkhind, Pune, India.
authors.forename: Jomon
authors.initials: J
authors.lastname: Joseph
mesh_terms: D000818:Animals; D002460:Cell Line; D005110:Extracellular Space / Q000378:metabolism*; D006801:Humans; D028884:Karyopherins / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism; D021381:Protein Transport; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D020931:ran GTP-Binding Protein / Q000378:metabolism*; D000097606:Exportin 1 Protein
chemical_list: D028884:Karyopherins; D018832:Molecular Chaperones; D028861:Nuclear Pore Complex Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D020931:ran GTP-Binding Protein; D000097606:Exportin 1 Protein; C094493:ran-binding protein 2