title: Vesicular and non-vesicular transport feed distinct glycosylation pathways in the Golgi.
abstract: Newly synthesized proteins and lipids are transported across the Golgi complex via different mechanisms whose respective roles are not completely clear. We previously identified a non-vesicular intra-Golgi transport pathway for glucosylceramide (GlcCer)--the common precursor of the different series of glycosphingolipids-that is operated by the cytosolic GlcCer-transfer protein FAPP2 (also known as PLEKHA8) (ref. 1). However, the molecular determinants of the FAPP2-mediated transfer of GlcCer from the cis-Golgi to the trans-Golgi network, as well as the physiological relevance of maintaining two parallel transport pathways of GlcCer--vesicular and non-vesicular--through the Golgi, remain poorly defined. Here, using mouse and cell models, we clarify the molecular mechanisms underlying the intra-Golgi vectorial transfer of GlcCer by FAPP2 and show that GlcCer is channelled by vesicular and non-vesicular transport to two topologically distinct glycosylation tracks in the Golgi cisternae and the trans-Golgi network, respectively. Our results indicate that the transport modality across the Golgi complex is a key determinant for the glycosylation pattern of a cargo and establish a new paradigm for the branching of the glycosphingolipid synthetic pathway.
authors.affiliation: Telethon Institute of Genetics and Medicine, Via Pietro Castellino 111, 80131 Naples, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: D'Angelo
authors.forename: Takefumi
authors.initials: T
authors.lastname: Uemura
authors.forename: Chia-Chen
authors.initials: CC
authors.lastname: Chuang
authors.forename: Elena
authors.initials: E
authors.lastname: Polishchuk
authors.forename: Michele
authors.initials: M
authors.lastname: Santoro
authors.forename: Henna
authors.initials: H
authors.lastname: Ohvo-Rekilä
authors.forename: Takashi
authors.initials: T
authors.lastname: Sato
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Tullio
authors.forename: Antonio
authors.initials: A
authors.lastname: Varriale
authors.forename: Sabato
authors.initials: S
authors.lastname: D'Auria
authors.forename: Tiziana
authors.initials: T
authors.lastname: Daniele
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Capuani
authors.forename: Ludger
authors.initials: L
authors.lastname: Johannes
authors.forename: Peter
authors.initials: P
authors.lastname: Mattjus
authors.forename: Maria
authors.initials: M
authors.lastname: Monti
authors.forename: Piero
authors.initials: P
authors.lastname: Pucci
authors.forename: Roger L
authors.initials: RL
authors.lastname: Williams
authors.forename: John E
authors.initials: JE
authors.lastname: Burke
authors.forename: Frances M
authors.initials: FM
authors.lastname: Platt
authors.forename: Akihiro
authors.initials: A
authors.lastname: Harada
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: De Matteis
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D005915:Globosides / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D005963:Glucosylceramides / Q000737:chemistry / Q000378:metabolism*; D006028:Glycosphingolipids / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D006031:Glycosylation; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D021601:trans-Golgi Network / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D005915:Globosides; D005963:Glucosylceramides; D006028:Glycosphingolipids; C487038:PLEKHA8 protein, human; D018129:Phosphatidylinositol Phosphates; C037178:phosphatidylinositol 4-phosphate
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