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Leucine-rich repeat kinase LRRK1 regulates endosomal trafficking of the EGF receptor

Activation of the epidermal growth factor receptor (EGFR) not only initiates multiple signal-transduction pathways, including the MAP kinase (MAPK) pathway, but also triggers trafficking events that relocalize receptors from the cell surface to intracellular endocytic compartments. In this paper, we...

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Autores principales: Hanafusa, Hiroshi, Ishikawa, Kouki, Kedashiro, Shin, Saigo, Tsukasa, Iemura, Shun-ichiro, Natsume, Tohru, Komada, Masayuki, Shibuya, Hiroshi, Nara, Atsuki, Matsumoto, Kunihiro
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3105304/
https://www.ncbi.nlm.nih.gov/pubmed/21245839
http://dx.doi.org/10.1038/ncomms1161
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author Hanafusa, Hiroshi
Ishikawa, Kouki
Kedashiro, Shin
Saigo, Tsukasa
Iemura, Shun-ichiro
Natsume, Tohru
Komada, Masayuki
Shibuya, Hiroshi
Nara, Atsuki
Matsumoto, Kunihiro
author_facet Hanafusa, Hiroshi
Ishikawa, Kouki
Kedashiro, Shin
Saigo, Tsukasa
Iemura, Shun-ichiro
Natsume, Tohru
Komada, Masayuki
Shibuya, Hiroshi
Nara, Atsuki
Matsumoto, Kunihiro
author_sort Hanafusa, Hiroshi
collection PubMed
description Activation of the epidermal growth factor receptor (EGFR) not only initiates multiple signal-transduction pathways, including the MAP kinase (MAPK) pathway, but also triggers trafficking events that relocalize receptors from the cell surface to intracellular endocytic compartments. In this paper, we demonstrate that leucine-rich repeat kinase LRRK1, which contains a MAPKKK-like kinase domain, forms a complex with activated EGFR through an interaction with Grb2. Subsequently, LRRK1 and epidermal growth factor (EGF) are internalized and co-localized in early endosomes. LRRK1 regulates EGFR transport from early to late endosomes and regulates the motility of EGF-containing early endosomes in a manner dependent on its kinase activity. Furthermore, LRRK1 serves as a scaffold facilitating the interaction of EGFR with the endosomal sorting complex required for transport-0 complex, thus enabling efficient sorting of EGFR to the inner vesicles of multivesicular bodies. Our findings provide the first evidence that a MAPKKK-like protein regulates the endosomal trafficking of EGFR.
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spelling pubmed-31053042011-06-01 Leucine-rich repeat kinase LRRK1 regulates endosomal trafficking of the EGF receptor Hanafusa, Hiroshi Ishikawa, Kouki Kedashiro, Shin Saigo, Tsukasa Iemura, Shun-ichiro Natsume, Tohru Komada, Masayuki Shibuya, Hiroshi Nara, Atsuki Matsumoto, Kunihiro Nat Commun Article Activation of the epidermal growth factor receptor (EGFR) not only initiates multiple signal-transduction pathways, including the MAP kinase (MAPK) pathway, but also triggers trafficking events that relocalize receptors from the cell surface to intracellular endocytic compartments. In this paper, we demonstrate that leucine-rich repeat kinase LRRK1, which contains a MAPKKK-like kinase domain, forms a complex with activated EGFR through an interaction with Grb2. Subsequently, LRRK1 and epidermal growth factor (EGF) are internalized and co-localized in early endosomes. LRRK1 regulates EGFR transport from early to late endosomes and regulates the motility of EGF-containing early endosomes in a manner dependent on its kinase activity. Furthermore, LRRK1 serves as a scaffold facilitating the interaction of EGFR with the endosomal sorting complex required for transport-0 complex, thus enabling efficient sorting of EGFR to the inner vesicles of multivesicular bodies. Our findings provide the first evidence that a MAPKKK-like protein regulates the endosomal trafficking of EGFR. Nature Publishing Group 2011-01-18 /pmc/articles/PMC3105304/ /pubmed/21245839 http://dx.doi.org/10.1038/ncomms1161 Text en Copyright © 2011, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Article
Hanafusa, Hiroshi
Ishikawa, Kouki
Kedashiro, Shin
Saigo, Tsukasa
Iemura, Shun-ichiro
Natsume, Tohru
Komada, Masayuki
Shibuya, Hiroshi
Nara, Atsuki
Matsumoto, Kunihiro
Leucine-rich repeat kinase LRRK1 regulates endosomal trafficking of the EGF receptor
title Leucine-rich repeat kinase LRRK1 regulates endosomal trafficking of the EGF receptor
title_full Leucine-rich repeat kinase LRRK1 regulates endosomal trafficking of the EGF receptor
title_fullStr Leucine-rich repeat kinase LRRK1 regulates endosomal trafficking of the EGF receptor
title_full_unstemmed Leucine-rich repeat kinase LRRK1 regulates endosomal trafficking of the EGF receptor
title_short Leucine-rich repeat kinase LRRK1 regulates endosomal trafficking of the EGF receptor
title_sort leucine-rich repeat kinase lrrk1 regulates endosomal trafficking of the egf receptor
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3105304/
https://www.ncbi.nlm.nih.gov/pubmed/21245839
http://dx.doi.org/10.1038/ncomms1161
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