Pre- and post-Golgi translocation of glucosylceramide in glycosphingolipid synthesis

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)


Interna författare/redaktörer


Publikationens författare: Halter D, Neumann S, van Dijk SM, Wolthoorn J, De Maziere AM, Vieira OV, Mattjus P, Klumperman J, van Meer G, Sprong H
Publiceringsår: 2007
Tidskrift: Journal of Cell Biology
Tidskriftsakronym: J CELL BIOL
Volym: 179
Nummer: 1
Artikelns första sida, sidnummer: 101
Artikelns sista sida, sidnummer: 115
Antal sidor: 115
ISSN: 0021-9525
eISSN: 1540-8140


Abstrakt

Glycosphingolipids are controlled by the spatial organization of their metabolism and by trans port specificity. Using immunoelectron microscopy, we localize to the Golgi stack the glycosyltransferases that produce glucosylceramide (GlcCer), lactosylceramide (LacCer), and GM3. GlcCer is synthesized on the cytosolic side and must translocate across to the Golgi lumen for LacCer synthesis. However, only very little natural GlcCer translocates across the Golgi in vitro. As GlcCer reaches the cell surface when Golgi vesicular trafficking is inhibited, it must translocate across a post-Golgi membrane. Concanamycin, a vacuolar proton pump inhibitor, blocks translocation independently of multidrug transporters that are known to translocate short-chain GlcCer. Concanamycin did not reduce LacCer and GM3 synthesis. Thus, GlcCer destined for glycolipid synthesis follows a different pathway and transports back into the endoplasmic reticulum (ER) via the late Golgi protein FAPP2. FAPP2 knockdown strongly reduces GM3 synthesis. Overall, we show that newly synthesized GlcCer enters two pathways: one toward the noncytosolic surface of a post-Golgi membrane and one via the ER toward the Golgi lumen LacCer synthase.

Senast uppdaterad 2019-13-12 vid 04:23