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The C10orf76–PI4KB axis orchestrates CERT-mediated ceramide trafficking to the distal Golgi

Phosphatidylinositol 4-monophosphate [PtdIns(4)P] is a precursor for various phosphoinositides but also a membrane-embedded component crucial for membrane contact sites (MCSs). Several lipid transfer proteins are recruited to MCSs by recognizing PtdIns(4)P; however, it remains poorly elucidated how...

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Autores principales: Mizuike, Aya, Sakai, Shota, Katoh, Kaoru, Yamaji, Toshiyuki, Hanada, Kentaro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10192306/
https://www.ncbi.nlm.nih.gov/pubmed/37195633
http://dx.doi.org/10.1083/jcb.202111069
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author Mizuike, Aya
Sakai, Shota
Katoh, Kaoru
Yamaji, Toshiyuki
Hanada, Kentaro
author_facet Mizuike, Aya
Sakai, Shota
Katoh, Kaoru
Yamaji, Toshiyuki
Hanada, Kentaro
author_sort Mizuike, Aya
collection PubMed
description Phosphatidylinositol 4-monophosphate [PtdIns(4)P] is a precursor for various phosphoinositides but also a membrane-embedded component crucial for membrane contact sites (MCSs). Several lipid transfer proteins are recruited to MCSs by recognizing PtdIns(4)P; however, it remains poorly elucidated how the production of PtdIns(4)P for lipid transport at MCSs is regulated. Following human genome-wide screening, we discovered that the PtdIns(4)P-related genes PI4KB, ACBD3, and C10orf76 are involved in endoplasmic reticulum-to-Golgi trafficking of ceramide by the ceramide transport protein CERT. CERT preferentially utilizes PtdIns(4)P generated by PI4KB recruited to the Golgi by C10orf76 rather than by ACBD3. Super-resolution microscopy observation revealed that C10orf76 predominantly localizes at distal Golgi regions, where sphingomyelin (SM) synthesis primarily occurs, while the majority of ACBD3 localizes at more proximal regions. This study provides a proof-of-concept that distinct pools of PtdIns(4)P are generated in different subregions, even within the same organelle, to facilitate interorganelle metabolic channeling for the ceramide-to-SM conversion.
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spelling pubmed-101923062023-05-19 The C10orf76–PI4KB axis orchestrates CERT-mediated ceramide trafficking to the distal Golgi Mizuike, Aya Sakai, Shota Katoh, Kaoru Yamaji, Toshiyuki Hanada, Kentaro J Cell Biol Article Phosphatidylinositol 4-monophosphate [PtdIns(4)P] is a precursor for various phosphoinositides but also a membrane-embedded component crucial for membrane contact sites (MCSs). Several lipid transfer proteins are recruited to MCSs by recognizing PtdIns(4)P; however, it remains poorly elucidated how the production of PtdIns(4)P for lipid transport at MCSs is regulated. Following human genome-wide screening, we discovered that the PtdIns(4)P-related genes PI4KB, ACBD3, and C10orf76 are involved in endoplasmic reticulum-to-Golgi trafficking of ceramide by the ceramide transport protein CERT. CERT preferentially utilizes PtdIns(4)P generated by PI4KB recruited to the Golgi by C10orf76 rather than by ACBD3. Super-resolution microscopy observation revealed that C10orf76 predominantly localizes at distal Golgi regions, where sphingomyelin (SM) synthesis primarily occurs, while the majority of ACBD3 localizes at more proximal regions. This study provides a proof-of-concept that distinct pools of PtdIns(4)P are generated in different subregions, even within the same organelle, to facilitate interorganelle metabolic channeling for the ceramide-to-SM conversion. Rockefeller University Press 2023-05-17 /pmc/articles/PMC10192306/ /pubmed/37195633 http://dx.doi.org/10.1083/jcb.202111069 Text en © 2023 Mizuike et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mizuike, Aya
Sakai, Shota
Katoh, Kaoru
Yamaji, Toshiyuki
Hanada, Kentaro
The C10orf76–PI4KB axis orchestrates CERT-mediated ceramide trafficking to the distal Golgi
title The C10orf76–PI4KB axis orchestrates CERT-mediated ceramide trafficking to the distal Golgi
title_full The C10orf76–PI4KB axis orchestrates CERT-mediated ceramide trafficking to the distal Golgi
title_fullStr The C10orf76–PI4KB axis orchestrates CERT-mediated ceramide trafficking to the distal Golgi
title_full_unstemmed The C10orf76–PI4KB axis orchestrates CERT-mediated ceramide trafficking to the distal Golgi
title_short The C10orf76–PI4KB axis orchestrates CERT-mediated ceramide trafficking to the distal Golgi
title_sort c10orf76–pi4kb axis orchestrates cert-mediated ceramide trafficking to the distal golgi
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10192306/
https://www.ncbi.nlm.nih.gov/pubmed/37195633
http://dx.doi.org/10.1083/jcb.202111069
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