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The activity of Sac1 across ER–TGN contact sites requires the four-phosphate-adaptor-protein-1

Phosphatidylinositol-4-phosphate (PI4P), a phosphoinositide with key roles in the Golgi complex, is made by Golgi-associated phosphatidylinositol-4 kinases and consumed by the 4-phosphatase Sac1 that, instead, is an ER membrane protein. Here, we show that the contact sites between the ER and the TGN...

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Autores principales: Venditti, Rossella, Masone, Maria Chiara, Rega, Laura Rita, Di Tullio, Giuseppe, Santoro, Michele, Polishchuk, Elena, Serrano, Ivan Castello, Olkkonen, Vesa M., Harada, Akihiro, Medina, Diego L., La Montagna, Raffaele, De Matteis, Maria Antonietta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400556/
https://www.ncbi.nlm.nih.gov/pubmed/30659099
http://dx.doi.org/10.1083/jcb.201812021
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author Venditti, Rossella
Masone, Maria Chiara
Rega, Laura Rita
Di Tullio, Giuseppe
Santoro, Michele
Polishchuk, Elena
Serrano, Ivan Castello
Olkkonen, Vesa M.
Harada, Akihiro
Medina, Diego L.
La Montagna, Raffaele
De Matteis, Maria Antonietta
author_facet Venditti, Rossella
Masone, Maria Chiara
Rega, Laura Rita
Di Tullio, Giuseppe
Santoro, Michele
Polishchuk, Elena
Serrano, Ivan Castello
Olkkonen, Vesa M.
Harada, Akihiro
Medina, Diego L.
La Montagna, Raffaele
De Matteis, Maria Antonietta
author_sort Venditti, Rossella
collection PubMed
description Phosphatidylinositol-4-phosphate (PI4P), a phosphoinositide with key roles in the Golgi complex, is made by Golgi-associated phosphatidylinositol-4 kinases and consumed by the 4-phosphatase Sac1 that, instead, is an ER membrane protein. Here, we show that the contact sites between the ER and the TGN (ERTGoCS) provide a spatial setting suitable for Sac1 to dephosphorylate PI4P at the TGN. The ERTGoCS, though necessary, are not sufficient for the phosphatase activity of Sac1 on TGN PI4P, since this needs the phosphatidyl-four-phosphate-adaptor-protein-1 (FAPP1). FAPP1 localizes at ERTGoCS, interacts with Sac1, and promotes its in-trans phosphatase activity in vitro. We envision that FAPP1, acting as a PI4P detector and adaptor, positions Sac1 close to TGN domains with elevated PI4P concentrations allowing PI4P consumption. Indeed, FAPP1 depletion induces an increase in TGN PI4P that leads to increased secretion of selected cargoes (e.g., ApoB100), indicating that FAPP1, by controlling PI4P levels, acts as a gatekeeper of Golgi exit.
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spelling pubmed-64005562019-09-04 The activity of Sac1 across ER–TGN contact sites requires the four-phosphate-adaptor-protein-1 Venditti, Rossella Masone, Maria Chiara Rega, Laura Rita Di Tullio, Giuseppe Santoro, Michele Polishchuk, Elena Serrano, Ivan Castello Olkkonen, Vesa M. Harada, Akihiro Medina, Diego L. La Montagna, Raffaele De Matteis, Maria Antonietta J Cell Biol Research Articles Phosphatidylinositol-4-phosphate (PI4P), a phosphoinositide with key roles in the Golgi complex, is made by Golgi-associated phosphatidylinositol-4 kinases and consumed by the 4-phosphatase Sac1 that, instead, is an ER membrane protein. Here, we show that the contact sites between the ER and the TGN (ERTGoCS) provide a spatial setting suitable for Sac1 to dephosphorylate PI4P at the TGN. The ERTGoCS, though necessary, are not sufficient for the phosphatase activity of Sac1 on TGN PI4P, since this needs the phosphatidyl-four-phosphate-adaptor-protein-1 (FAPP1). FAPP1 localizes at ERTGoCS, interacts with Sac1, and promotes its in-trans phosphatase activity in vitro. We envision that FAPP1, acting as a PI4P detector and adaptor, positions Sac1 close to TGN domains with elevated PI4P concentrations allowing PI4P consumption. Indeed, FAPP1 depletion induces an increase in TGN PI4P that leads to increased secretion of selected cargoes (e.g., ApoB100), indicating that FAPP1, by controlling PI4P levels, acts as a gatekeeper of Golgi exit. Rockefeller University Press 2019-03-04 /pmc/articles/PMC6400556/ /pubmed/30659099 http://dx.doi.org/10.1083/jcb.201812021 Text en © 2019 Venditti et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Venditti, Rossella
Masone, Maria Chiara
Rega, Laura Rita
Di Tullio, Giuseppe
Santoro, Michele
Polishchuk, Elena
Serrano, Ivan Castello
Olkkonen, Vesa M.
Harada, Akihiro
Medina, Diego L.
La Montagna, Raffaele
De Matteis, Maria Antonietta
The activity of Sac1 across ER–TGN contact sites requires the four-phosphate-adaptor-protein-1
title The activity of Sac1 across ER–TGN contact sites requires the four-phosphate-adaptor-protein-1
title_full The activity of Sac1 across ER–TGN contact sites requires the four-phosphate-adaptor-protein-1
title_fullStr The activity of Sac1 across ER–TGN contact sites requires the four-phosphate-adaptor-protein-1
title_full_unstemmed The activity of Sac1 across ER–TGN contact sites requires the four-phosphate-adaptor-protein-1
title_short The activity of Sac1 across ER–TGN contact sites requires the four-phosphate-adaptor-protein-1
title_sort activity of sac1 across er–tgn contact sites requires the four-phosphate-adaptor-protein-1
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400556/
https://www.ncbi.nlm.nih.gov/pubmed/30659099
http://dx.doi.org/10.1083/jcb.201812021
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