Glycosphingolipid synthesis requires FAPP2 transfer of glucosylceramide.

The molecular machinery responsible for the generation of transport carriers moving from the Golgi complex to the plasma membrane relies on a tight interplay between proteins and lipids. Among the lipid-binding proteins of this machinery, we previously identified the four-phosphate adaptor protein F...

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Main Authors: D'Angelo, G, Polishchuk, E, Di Tullio, G, Santoro, M, Di Campli, A, Godi, A, West, G, Bielawski, J, Chuang, C, van der Spoel, A, Platt, F, Hannun, Y, Polishchuk, R, Mattjus, P, Matteis, D
Format: Journal article
Language:English
Published: 2007
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author D'Angelo, G
Polishchuk, E
Di Tullio, G
Santoro, M
Di Campli, A
Godi, A
West, G
Bielawski, J
Chuang, C
van der Spoel, A
Platt, F
Hannun, Y
Polishchuk, R
Mattjus, P
Matteis, D
author_facet D'Angelo, G
Polishchuk, E
Di Tullio, G
Santoro, M
Di Campli, A
Godi, A
West, G
Bielawski, J
Chuang, C
van der Spoel, A
Platt, F
Hannun, Y
Polishchuk, R
Mattjus, P
Matteis, D
author_sort D'Angelo, G
collection OXFORD
description The molecular machinery responsible for the generation of transport carriers moving from the Golgi complex to the plasma membrane relies on a tight interplay between proteins and lipids. Among the lipid-binding proteins of this machinery, we previously identified the four-phosphate adaptor protein FAPP2, the pleckstrin homology domain of which binds phosphatidylinositol 4-phosphate and the small GTPase ARF1. FAPP2 also possesses a glycolipid-transfer-protein homology domain. Here we show that human FAPP2 is a glucosylceramide-transfer protein that has a pivotal role in the synthesis of complex glycosphingolipids, key structural and signalling components of the plasma membrane. The requirement for FAPP2 makes the whole glycosphingolipid synthetic pathway sensitive to regulation by phosphatidylinositol 4-phosphate and ARF1. Thus, by coupling the synthesis of glycosphingolipids with their export to the cell surface, FAPP2 emerges as crucial in determining the lipid identity and composition of the plasma membrane.
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spelling oxford-uuid:9c8b4ab1-5f60-4fba-89ff-57d8148c21e42022-03-27T00:36:46ZGlycosphingolipid synthesis requires FAPP2 transfer of glucosylceramide.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9c8b4ab1-5f60-4fba-89ff-57d8148c21e4EnglishSymplectic Elements at Oxford2007D'Angelo, GPolishchuk, EDi Tullio, GSantoro, MDi Campli, AGodi, AWest, GBielawski, JChuang, Cvan der Spoel, APlatt, FHannun, YPolishchuk, RMattjus, PMatteis, DThe molecular machinery responsible for the generation of transport carriers moving from the Golgi complex to the plasma membrane relies on a tight interplay between proteins and lipids. Among the lipid-binding proteins of this machinery, we previously identified the four-phosphate adaptor protein FAPP2, the pleckstrin homology domain of which binds phosphatidylinositol 4-phosphate and the small GTPase ARF1. FAPP2 also possesses a glycolipid-transfer-protein homology domain. Here we show that human FAPP2 is a glucosylceramide-transfer protein that has a pivotal role in the synthesis of complex glycosphingolipids, key structural and signalling components of the plasma membrane. The requirement for FAPP2 makes the whole glycosphingolipid synthetic pathway sensitive to regulation by phosphatidylinositol 4-phosphate and ARF1. Thus, by coupling the synthesis of glycosphingolipids with their export to the cell surface, FAPP2 emerges as crucial in determining the lipid identity and composition of the plasma membrane.
spellingShingle D'Angelo, G
Polishchuk, E
Di Tullio, G
Santoro, M
Di Campli, A
Godi, A
West, G
Bielawski, J
Chuang, C
van der Spoel, A
Platt, F
Hannun, Y
Polishchuk, R
Mattjus, P
Matteis, D
Glycosphingolipid synthesis requires FAPP2 transfer of glucosylceramide.
title Glycosphingolipid synthesis requires FAPP2 transfer of glucosylceramide.
title_full Glycosphingolipid synthesis requires FAPP2 transfer of glucosylceramide.
title_fullStr Glycosphingolipid synthesis requires FAPP2 transfer of glucosylceramide.
title_full_unstemmed Glycosphingolipid synthesis requires FAPP2 transfer of glucosylceramide.
title_short Glycosphingolipid synthesis requires FAPP2 transfer of glucosylceramide.
title_sort glycosphingolipid synthesis requires fapp2 transfer of glucosylceramide
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