Publication Date:
2013-08-06
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉D'Angelo, Giovanni -- Uemura, Takefumi -- Chuang, Chia-Chen -- Polishchuk, Elena -- Santoro, Michele -- Ohvo-Rekila, Henna -- Sato, Takashi -- Di Tullio, Giuseppe -- Varriale, Antonio -- D'Auria, Sabato -- Daniele, Tiziana -- Capuani, Fabrizio -- Johannes, Ludger -- Mattjus, Peter -- Monti, Maria -- Pucci, Piero -- Williams, Roger L -- Burke, John E -- Platt, Frances M -- Harada, Akihiro -- De Matteis, Maria Antonietta -- MC_U105184308/Medical Research Council/United Kingdom -- PG/11/109/29247/British Heart Foundation/United Kingdom -- TGM11CB1/Telethon/Italy -- England -- Nature. 2013 Sep 5;501(7465):116-20. doi: 10.1038/nature12423. Epub 2013 Aug 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Telethon Institute of Genetics and Medicine, Via Pietro Castellino 111, 80131 Naples, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23913272" target="_blank"〉PubMed〈/a〉
Keywords:
Adaptor Proteins, Signal Transducing/genetics/metabolism
;
Animals
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Biological Transport
;
Cell Line
;
Globosides/biosynthesis/chemistry/metabolism
;
Glucosylceramides/chemistry/*metabolism
;
Glycosphingolipids/biosynthesis/chemistry/metabolism
;
*Glycosylation
;
Golgi Apparatus/*metabolism
;
Humans
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Mice
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Mice, Inbred C57BL
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Phosphatidylinositol Phosphates/metabolism
;
trans-Golgi Network/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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