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

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Venditti , R , Masone , M C , Rega , L R , Di Tullio , G , Santoro , M , Polishchuk , E , Serrano , I C , Olkkonen , V M , Harada , A , Medina , D L , La Montagna , R & De Matteis , M A 2019 , ' The activity of Sac1 across ER-TGN contact sites requires the four-phosphate-adaptor-protein-1 ' , Journal of Cell Biology , vol. 218 , no. 3 , pp. 783-797 . https://doi.org/10.1083/jcb.201812021

Title: The activity of Sac1 across ER-TGN contact sites requires the four-phosphate-adaptor-protein-1
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
Contributor organization: Medicum
Department of Anatomy
Faculty of Medicine
University of Helsinki
Date: 2019-03
Language: eng
Number of pages: 15
Belongs to series: Journal of Cell Biology
ISSN: 0021-9525
DOI: https://doi.org/10.1083/jcb.201812021
URI: http://hdl.handle.net/10138/305644
Abstract: 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.
Subject: PHOSPHATASE SAC1
GOLGI
BINDING
PROTEIN
MULTIPLE
PHOSPHATIDYLINOSITOL-4-PHOSPHATE
LOCALIZATION
TRAFFICKING
TRANSPORT
EXPORT
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Rights: cc_by_nc_sa
Usage restriction: openAccess
Self-archived version: publishedVersion


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