title: Ganglioside GD3 traffics from the trans-Golgi network to plasma membrane by a Rab11-independent and brefeldin A-insensitive exocytic pathway.
abstract: Gangliosides, complex glycosphingolipids containing sialic acids, have been found to reside in glycosphingolipid-enriched microdomains (GEM) at the plasma membrane. They are synthesized in the lumen of the Golgi complex and appear unable to translocate from the lumenal toward the cytosolic surface of Golgi membrane to access the monomeric lipid transport. As a consequence, they can only leave the Golgi complex via the lumenal surface of transport vesicles. In this work we analyzed the exocytic transport of the disialo ganglioside GD3 from trans-Golgi network (TGN) to plasma membrane in CHO-K1 cells by immunodetection of endogenously synthesized GD3. We found that ganglioside GD3, unlike another luminal membrane-bounded lipid (glycosylphosphatidylinositol-anchored protein), did not partition into GEM domains in the Golgi complex and trafficked from TGN to plasma membrane by a brefeldin A-insensitive exocytic pathway. Moreover, a dominant negative form of Rab11, which prevents exit of vesicular stomatitis virus glycoprotein from the Golgi complex, did not influence the capacity of GD3 to reach the cell surface. Our results strongly support the notion that most ganglioside GD3 traffics from the TGN to the plasma membrane by a non-conventional vesicular pathway where lateral membrane segregation of vesicular stomatitis virus glycoprotein (non-GEM resident) and glycosylphosphatidylinositol-anchored proteins (GEM resident) from GD3 is required before exiting TGN.
authors.affiliation: Centro de Investigaciones en Química Biológica de Córdoba, CIQUIBIC (UNC-CONICET), Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, 5000 Córdoba, Argentina.
authors.forename: Pilar Maria
authors.initials: PM
authors.lastname: Crespo
authors.forename: Ramiro
authors.initials: R
authors.lastname: Iglesias-Bartolomé
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Daniotti
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D020126:Brefeldin A / Q000378:metabolism*; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism*; D002518:Ceramides / Q000378:metabolism; D006224:Cricetinae; D003902:Detergents / Q000378:metabolism; D005089:Exocytosis / Q000502:physiology*; D005732:Gangliosides / Q000378:metabolism*; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D017830:Octoxynol / Q000378:metabolism; D011412:Propanolamines / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000378:metabolism*; D011759:Pyrrolidines / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D021601:trans-Golgi Network / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
chemical_list: D020126:Brefeldin A; D002518:Ceramides; D003902:Detergents; D005732:Gangliosides; D017261:Glycosylphosphatidylinositols; D008562:Membrane Glycoproteins; D017830:Octoxynol; D011412:Propanolamines; D011500:Protein Synthesis Inhibitors; D011759:Pyrrolidines; D011993:Recombinant Fusion Proteins; D013109:Sphingomyelins; D014759:Viral Envelope Proteins; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C110417:1-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol; C028391:G protein, vesicular stomatitis virus; C026226:ganglioside, GD3