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Negative regulation of phosphatidylinositol 3-phosphate levels in early-to-late endosome conversion
Phosphatidylinositol 3-phosphate (PtdIns3P) plays a central role in endosome fusion, recycling, sorting, and early-to-late endosome conversion, but the mechanisms that determine how the correct endosomal PtdIns3P level is achieved remain largely elusive. Here we identify two new factors, SORF-1 and...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4738380/ https://www.ncbi.nlm.nih.gov/pubmed/26783301 http://dx.doi.org/10.1083/jcb.201506081 |
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author | Liu, Kai Jian, Youli Sun, Xiaojuan Yang, Chengkui Gao, Zhiyang Zhang, Zhili Liu, Xuezhao Li, Yang Xu, Jing Jing, Yudong Mitani, Shohei He, Sudan Yang, Chonglin |
author_facet | Liu, Kai Jian, Youli Sun, Xiaojuan Yang, Chengkui Gao, Zhiyang Zhang, Zhili Liu, Xuezhao Li, Yang Xu, Jing Jing, Yudong Mitani, Shohei He, Sudan Yang, Chonglin |
author_sort | Liu, Kai |
collection | PubMed |
description | Phosphatidylinositol 3-phosphate (PtdIns3P) plays a central role in endosome fusion, recycling, sorting, and early-to-late endosome conversion, but the mechanisms that determine how the correct endosomal PtdIns3P level is achieved remain largely elusive. Here we identify two new factors, SORF-1 and SORF-2, as essential PtdIns3P regulators in Caenorhabditis elegans. Loss of sorf-1 or sorf-2 leads to greatly elevated endosomal PtdIns3P, which drives excessive fusion of early endosomes. sorf-1 and sorf-2 function coordinately with Rab switching genes to inhibit synthesis of PtdIns3P, allowing its turnover for endosome conversion. SORF-1 and SORF-2 act in a complex with BEC-1/Beclin1, and their loss causes elevated activity of the phosphatidylinositol 3-kinase (PI3K) complex. In mammalian cells, inactivation of WDR91 and WDR81, the homologs of SORF-1 and SORF-2, induces Beclin1-dependent enlargement of PtdIns3P-enriched endosomes and defective degradation of epidermal growth factor receptor. WDR91 and WDR81 interact with Beclin1 and inhibit PI3K complex activity. These findings reveal a conserved mechanism that controls appropriate PtdIns3P levels in early-to-late endosome conversion. |
format | Online Article Text |
id | pubmed-4738380 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-47383802016-07-18 Negative regulation of phosphatidylinositol 3-phosphate levels in early-to-late endosome conversion Liu, Kai Jian, Youli Sun, Xiaojuan Yang, Chengkui Gao, Zhiyang Zhang, Zhili Liu, Xuezhao Li, Yang Xu, Jing Jing, Yudong Mitani, Shohei He, Sudan Yang, Chonglin J Cell Biol Research Articles Phosphatidylinositol 3-phosphate (PtdIns3P) plays a central role in endosome fusion, recycling, sorting, and early-to-late endosome conversion, but the mechanisms that determine how the correct endosomal PtdIns3P level is achieved remain largely elusive. Here we identify two new factors, SORF-1 and SORF-2, as essential PtdIns3P regulators in Caenorhabditis elegans. Loss of sorf-1 or sorf-2 leads to greatly elevated endosomal PtdIns3P, which drives excessive fusion of early endosomes. sorf-1 and sorf-2 function coordinately with Rab switching genes to inhibit synthesis of PtdIns3P, allowing its turnover for endosome conversion. SORF-1 and SORF-2 act in a complex with BEC-1/Beclin1, and their loss causes elevated activity of the phosphatidylinositol 3-kinase (PI3K) complex. In mammalian cells, inactivation of WDR91 and WDR81, the homologs of SORF-1 and SORF-2, induces Beclin1-dependent enlargement of PtdIns3P-enriched endosomes and defective degradation of epidermal growth factor receptor. WDR91 and WDR81 interact with Beclin1 and inhibit PI3K complex activity. These findings reveal a conserved mechanism that controls appropriate PtdIns3P levels in early-to-late endosome conversion. The Rockefeller University Press 2016-01-18 /pmc/articles/PMC4738380/ /pubmed/26783301 http://dx.doi.org/10.1083/jcb.201506081 Text en © 2016 Liu et al. 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 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Liu, Kai Jian, Youli Sun, Xiaojuan Yang, Chengkui Gao, Zhiyang Zhang, Zhili Liu, Xuezhao Li, Yang Xu, Jing Jing, Yudong Mitani, Shohei He, Sudan Yang, Chonglin Negative regulation of phosphatidylinositol 3-phosphate levels in early-to-late endosome conversion |
title | Negative regulation of phosphatidylinositol 3-phosphate levels in early-to-late endosome conversion |
title_full | Negative regulation of phosphatidylinositol 3-phosphate levels in early-to-late endosome conversion |
title_fullStr | Negative regulation of phosphatidylinositol 3-phosphate levels in early-to-late endosome conversion |
title_full_unstemmed | Negative regulation of phosphatidylinositol 3-phosphate levels in early-to-late endosome conversion |
title_short | Negative regulation of phosphatidylinositol 3-phosphate levels in early-to-late endosome conversion |
title_sort | negative regulation of phosphatidylinositol 3-phosphate levels in early-to-late endosome conversion |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4738380/ https://www.ncbi.nlm.nih.gov/pubmed/26783301 http://dx.doi.org/10.1083/jcb.201506081 |
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