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EHBP1L1 coordinates Rab8 and Bin1 to regulate apical-directed transport in polarized epithelial cells
The highly conserved Rab guanosine triphosphatase (GTPase) Rab8 plays a role in exocytosis toward the polarized plasma membrane in eukaryotic cells. In murine Rab8-deficient small intestine cells, apical proteins are missorted into lysosomes. In this study, we identified a novel Rab8-interacting pro...
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/PMC4739609/ https://www.ncbi.nlm.nih.gov/pubmed/26833786 http://dx.doi.org/10.1083/jcb.201508086 |
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author | Nakajo, Atsuhiro Yoshimura, Shin-ichiro Togawa, Hiroko Kunii, Masataka Iwano, Tomohiko Izumi, Ayaka Noguchi, Yuria Watanabe, Ayako Goto, Ayako Sato, Toshiro Harada, Akihiro |
author_facet | Nakajo, Atsuhiro Yoshimura, Shin-ichiro Togawa, Hiroko Kunii, Masataka Iwano, Tomohiko Izumi, Ayaka Noguchi, Yuria Watanabe, Ayako Goto, Ayako Sato, Toshiro Harada, Akihiro |
author_sort | Nakajo, Atsuhiro |
collection | PubMed |
description | The highly conserved Rab guanosine triphosphatase (GTPase) Rab8 plays a role in exocytosis toward the polarized plasma membrane in eukaryotic cells. In murine Rab8-deficient small intestine cells, apical proteins are missorted into lysosomes. In this study, we identified a novel Rab8-interacting protein complex containing an EH domain–binding protein 1–like 1 (EHBP1L1), Bin1/amphiphysin II, and dynamin. Biochemical analyses showed that EHBP1L1 directly bound to GTP-loaded Rab8 and Bin1. The spatial dependency of these complexes at the endocytic recycling compartment (ERC) was demonstrated through overexpression and knockdown experiments. EHBP1L1- or Bin1-depleted or dynamin-inhibited small intestine organoids significantly accumulated apical membrane proteins but not basolateral membrane proteins in lysosomes. Furthermore, in EHBP1L1-deficient mice, small intestine cells displayed truncated and sparse microvilli, suggesting that EHBP1L1 maintains the apical plasma membrane by regulating apical transport. In summary, our data demonstrate that EHBP1L1 links Rab8 and the Bin1–dynamin complex, which generates membrane curvature and excises the vesicle at the ERC for apical transport. |
format | Online Article Text |
id | pubmed-4739609 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-47396092016-08-01 EHBP1L1 coordinates Rab8 and Bin1 to regulate apical-directed transport in polarized epithelial cells Nakajo, Atsuhiro Yoshimura, Shin-ichiro Togawa, Hiroko Kunii, Masataka Iwano, Tomohiko Izumi, Ayaka Noguchi, Yuria Watanabe, Ayako Goto, Ayako Sato, Toshiro Harada, Akihiro J Cell Biol Research Articles The highly conserved Rab guanosine triphosphatase (GTPase) Rab8 plays a role in exocytosis toward the polarized plasma membrane in eukaryotic cells. In murine Rab8-deficient small intestine cells, apical proteins are missorted into lysosomes. In this study, we identified a novel Rab8-interacting protein complex containing an EH domain–binding protein 1–like 1 (EHBP1L1), Bin1/amphiphysin II, and dynamin. Biochemical analyses showed that EHBP1L1 directly bound to GTP-loaded Rab8 and Bin1. The spatial dependency of these complexes at the endocytic recycling compartment (ERC) was demonstrated through overexpression and knockdown experiments. EHBP1L1- or Bin1-depleted or dynamin-inhibited small intestine organoids significantly accumulated apical membrane proteins but not basolateral membrane proteins in lysosomes. Furthermore, in EHBP1L1-deficient mice, small intestine cells displayed truncated and sparse microvilli, suggesting that EHBP1L1 maintains the apical plasma membrane by regulating apical transport. In summary, our data demonstrate that EHBP1L1 links Rab8 and the Bin1–dynamin complex, which generates membrane curvature and excises the vesicle at the ERC for apical transport. The Rockefeller University Press 2016-02-01 /pmc/articles/PMC4739609/ /pubmed/26833786 http://dx.doi.org/10.1083/jcb.201508086 Text en © 2016 Nakajo 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 Nakajo, Atsuhiro Yoshimura, Shin-ichiro Togawa, Hiroko Kunii, Masataka Iwano, Tomohiko Izumi, Ayaka Noguchi, Yuria Watanabe, Ayako Goto, Ayako Sato, Toshiro Harada, Akihiro EHBP1L1 coordinates Rab8 and Bin1 to regulate apical-directed transport in polarized epithelial cells |
title | EHBP1L1 coordinates Rab8 and Bin1 to regulate apical-directed transport in polarized epithelial cells |
title_full | EHBP1L1 coordinates Rab8 and Bin1 to regulate apical-directed transport in polarized epithelial cells |
title_fullStr | EHBP1L1 coordinates Rab8 and Bin1 to regulate apical-directed transport in polarized epithelial cells |
title_full_unstemmed | EHBP1L1 coordinates Rab8 and Bin1 to regulate apical-directed transport in polarized epithelial cells |
title_short | EHBP1L1 coordinates Rab8 and Bin1 to regulate apical-directed transport in polarized epithelial cells |
title_sort | ehbp1l1 coordinates rab8 and bin1 to regulate apical-directed transport in polarized epithelial cells |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4739609/ https://www.ncbi.nlm.nih.gov/pubmed/26833786 http://dx.doi.org/10.1083/jcb.201508086 |
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