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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...

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Autores principales: Nakajo, Atsuhiro, Yoshimura, Shin-ichiro, Togawa, Hiroko, Kunii, Masataka, Iwano, Tomohiko, Izumi, Ayaka, Noguchi, Yuria, Watanabe, Ayako, Goto, Ayako, Sato, Toshiro, Harada, Akihiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2016
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.
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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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