Regulation of CCR7-dependent cell migration through CCR7 homodimer formation

Abstract The chemokine receptor CCR7 contributes to various physiological and pathological processes including T cell maturation, T cell migration from the blood into secondary lymphoid tissues, and tumor cell metastasis to lymph nodes. Although a previous study suggested that the efficacy of CCR7 l...

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Autores principales:	Daichi Kobayashi, Masataka Endo, Hirotaka Ochi, Hironobu Hojo, Masayuki Miyasaka, Haruko Hayasaka
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/db09bcb04bcd4684b0490d08f757b874
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spelling	oai:doaj.org-article:db09bcb04bcd4684b0490d08f757b8742021-12-02T16:08:21ZRegulation of CCR7-dependent cell migration through CCR7 homodimer formation10.1038/s41598-017-09113-42045-2322https://doaj.org/article/db09bcb04bcd4684b0490d08f757b8742017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09113-4https://doaj.org/toc/2045-2322Abstract The chemokine receptor CCR7 contributes to various physiological and pathological processes including T cell maturation, T cell migration from the blood into secondary lymphoid tissues, and tumor cell metastasis to lymph nodes. Although a previous study suggested that the efficacy of CCR7 ligand-dependent T cell migration correlates with CCR7 homo- and heterodimer formation, the exact extent of contribution of the CCR7 dimerization remains unclear. Here, by inducing or disrupting CCR7 dimers, we demonstrated a direct contribution of CCR7 homodimerization to CCR7-dependent cell migration and signaling. Induction of stable CCR7 homodimerization resulted in enhanced CCR7-dependent cell migration and CCL19 binding, whereas induction of CXCR4/CCR7 heterodimerization did not. In contrast, dissociation of CCR7 homodimerization by a novel CCR7-derived synthetic peptide attenuated CCR7-dependent cell migration, ligand-dependent CCR7 internalization, ligand-induced actin rearrangement, and Akt and Erk signaling in CCR7-expressing cells. Our study indicates that CCR7 homodimerization critically regulates CCR7 ligand-dependent cell migration and intracellular signaling in multiple cell types.Daichi KobayashiMasataka EndoHirotaka OchiHironobu HojoMasayuki MiyasakaHaruko HayasakaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daichi Kobayashi Masataka Endo Hirotaka Ochi Hironobu Hojo Masayuki Miyasaka Haruko Hayasaka Regulation of CCR7-dependent cell migration through CCR7 homodimer formation
description	Abstract The chemokine receptor CCR7 contributes to various physiological and pathological processes including T cell maturation, T cell migration from the blood into secondary lymphoid tissues, and tumor cell metastasis to lymph nodes. Although a previous study suggested that the efficacy of CCR7 ligand-dependent T cell migration correlates with CCR7 homo- and heterodimer formation, the exact extent of contribution of the CCR7 dimerization remains unclear. Here, by inducing or disrupting CCR7 dimers, we demonstrated a direct contribution of CCR7 homodimerization to CCR7-dependent cell migration and signaling. Induction of stable CCR7 homodimerization resulted in enhanced CCR7-dependent cell migration and CCL19 binding, whereas induction of CXCR4/CCR7 heterodimerization did not. In contrast, dissociation of CCR7 homodimerization by a novel CCR7-derived synthetic peptide attenuated CCR7-dependent cell migration, ligand-dependent CCR7 internalization, ligand-induced actin rearrangement, and Akt and Erk signaling in CCR7-expressing cells. Our study indicates that CCR7 homodimerization critically regulates CCR7 ligand-dependent cell migration and intracellular signaling in multiple cell types.
format	article
author	Daichi Kobayashi Masataka Endo Hirotaka Ochi Hironobu Hojo Masayuki Miyasaka Haruko Hayasaka
author_facet	Daichi Kobayashi Masataka Endo Hirotaka Ochi Hironobu Hojo Masayuki Miyasaka Haruko Hayasaka
author_sort	Daichi Kobayashi
title	Regulation of CCR7-dependent cell migration through CCR7 homodimer formation
title_short	Regulation of CCR7-dependent cell migration through CCR7 homodimer formation
title_full	Regulation of CCR7-dependent cell migration through CCR7 homodimer formation
title_fullStr	Regulation of CCR7-dependent cell migration through CCR7 homodimer formation
title_full_unstemmed	Regulation of CCR7-dependent cell migration through CCR7 homodimer formation
title_sort	regulation of ccr7-dependent cell migration through ccr7 homodimer formation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/db09bcb04bcd4684b0490d08f757b874
work_keys_str_mv	AT daichikobayashi regulationofccr7dependentcellmigrationthroughccr7homodimerformation AT masatakaendo regulationofccr7dependentcellmigrationthroughccr7homodimerformation AT hirotakaochi regulationofccr7dependentcellmigrationthroughccr7homodimerformation AT hironobuhojo regulationofccr7dependentcellmigrationthroughccr7homodimerformation AT masayukimiyasaka regulationofccr7dependentcellmigrationthroughccr7homodimerformation AT harukohayasaka regulationofccr7dependentcellmigrationthroughccr7homodimerformation
_version_	1718384562802786304

Regulation of CCR7-dependent cell migration through CCR7 homodimer formation

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