Cargando…
Circadian clock component PERIOD2 regulates diurnal expression of Na(+)/H(+) exchanger regulatory factor-1 and its scaffolding function
A number of diverse cell-surface proteins are anchored to the cytoskeleton via scaffold proteins. Na(+)/H(+) exchanger regulatory factor-1 (NHERF1), encoded by the Slc9a3r1 gene, functions as a scaffold protein, which is implicated in the regulation of membrane expression of various cell-surface pro...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5998136/ https://www.ncbi.nlm.nih.gov/pubmed/29899468 http://dx.doi.org/10.1038/s41598-018-27280-w |
_version_ | 1783331189741846528 |
---|---|
author | Tsurudome, Yuya Koyanagi, Satoru Kanemitsu, Takumi Katamune, Chiharu Oda, Masayuki Kanado, Yuki Kato, Mizuki Morita, Akari Tahara, Yu Matsunaga, Naoya Shibata, Shigenobu Ohdo, Shigehiro |
author_facet | Tsurudome, Yuya Koyanagi, Satoru Kanemitsu, Takumi Katamune, Chiharu Oda, Masayuki Kanado, Yuki Kato, Mizuki Morita, Akari Tahara, Yu Matsunaga, Naoya Shibata, Shigenobu Ohdo, Shigehiro |
author_sort | Tsurudome, Yuya |
collection | PubMed |
description | A number of diverse cell-surface proteins are anchored to the cytoskeleton via scaffold proteins. Na(+)/H(+) exchanger regulatory factor-1 (NHERF1), encoded by the Slc9a3r1 gene, functions as a scaffold protein, which is implicated in the regulation of membrane expression of various cell-surface proteins. Here, we demonstrate that the circadian clock component PERIOD2 (PER2) modulates transcription of the mouse Slc9a3r1 gene, generating diurnal accumulation of NHERF1 in the mouse liver. Basal expression of Slc9a3r1 was dependent on transcriptional activation by p65/p50. PER2 bound to p65 protein and prevented p65/p50-mediated transactivation of Slc9a3r1. The time-dependent interaction between PER2 and p65 underlay diurnal oscillation in the hepatic expression of Slc9a3r1/NHERF1. The results of immunoprecipitation experiments and liquid chromatography-mass spectrometry analysis of mouse liver revealed that NHERF1 time-dependently interacted with fatty acid transport protein-5 (FATP5). Temporary accumulation of NHERF1 protein stabilized plasmalemmal localization of FATP5, thereby enhancing hepatic uptake of fatty acids at certain times of the day. Our results suggest an unacknowledged role for PER2 in regulating the diurnal expression of NHERF1 in mouse liver. This machinery also contributed to diurnal changes in the ability of hepatic cells to uptake fatty acids. |
format | Online Article Text |
id | pubmed-5998136 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-59981362018-06-21 Circadian clock component PERIOD2 regulates diurnal expression of Na(+)/H(+) exchanger regulatory factor-1 and its scaffolding function Tsurudome, Yuya Koyanagi, Satoru Kanemitsu, Takumi Katamune, Chiharu Oda, Masayuki Kanado, Yuki Kato, Mizuki Morita, Akari Tahara, Yu Matsunaga, Naoya Shibata, Shigenobu Ohdo, Shigehiro Sci Rep Article A number of diverse cell-surface proteins are anchored to the cytoskeleton via scaffold proteins. Na(+)/H(+) exchanger regulatory factor-1 (NHERF1), encoded by the Slc9a3r1 gene, functions as a scaffold protein, which is implicated in the regulation of membrane expression of various cell-surface proteins. Here, we demonstrate that the circadian clock component PERIOD2 (PER2) modulates transcription of the mouse Slc9a3r1 gene, generating diurnal accumulation of NHERF1 in the mouse liver. Basal expression of Slc9a3r1 was dependent on transcriptional activation by p65/p50. PER2 bound to p65 protein and prevented p65/p50-mediated transactivation of Slc9a3r1. The time-dependent interaction between PER2 and p65 underlay diurnal oscillation in the hepatic expression of Slc9a3r1/NHERF1. The results of immunoprecipitation experiments and liquid chromatography-mass spectrometry analysis of mouse liver revealed that NHERF1 time-dependently interacted with fatty acid transport protein-5 (FATP5). Temporary accumulation of NHERF1 protein stabilized plasmalemmal localization of FATP5, thereby enhancing hepatic uptake of fatty acids at certain times of the day. Our results suggest an unacknowledged role for PER2 in regulating the diurnal expression of NHERF1 in mouse liver. This machinery also contributed to diurnal changes in the ability of hepatic cells to uptake fatty acids. Nature Publishing Group UK 2018-06-13 /pmc/articles/PMC5998136/ /pubmed/29899468 http://dx.doi.org/10.1038/s41598-018-27280-w Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Tsurudome, Yuya Koyanagi, Satoru Kanemitsu, Takumi Katamune, Chiharu Oda, Masayuki Kanado, Yuki Kato, Mizuki Morita, Akari Tahara, Yu Matsunaga, Naoya Shibata, Shigenobu Ohdo, Shigehiro Circadian clock component PERIOD2 regulates diurnal expression of Na(+)/H(+) exchanger regulatory factor-1 and its scaffolding function |
title | Circadian clock component PERIOD2 regulates diurnal expression of Na(+)/H(+) exchanger regulatory factor-1 and its scaffolding function |
title_full | Circadian clock component PERIOD2 regulates diurnal expression of Na(+)/H(+) exchanger regulatory factor-1 and its scaffolding function |
title_fullStr | Circadian clock component PERIOD2 regulates diurnal expression of Na(+)/H(+) exchanger regulatory factor-1 and its scaffolding function |
title_full_unstemmed | Circadian clock component PERIOD2 regulates diurnal expression of Na(+)/H(+) exchanger regulatory factor-1 and its scaffolding function |
title_short | Circadian clock component PERIOD2 regulates diurnal expression of Na(+)/H(+) exchanger regulatory factor-1 and its scaffolding function |
title_sort | circadian clock component period2 regulates diurnal expression of na(+)/h(+) exchanger regulatory factor-1 and its scaffolding function |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5998136/ https://www.ncbi.nlm.nih.gov/pubmed/29899468 http://dx.doi.org/10.1038/s41598-018-27280-w |
work_keys_str_mv | AT tsurudomeyuya circadianclockcomponentperiod2regulatesdiurnalexpressionofnahexchangerregulatoryfactor1anditsscaffoldingfunction AT koyanagisatoru circadianclockcomponentperiod2regulatesdiurnalexpressionofnahexchangerregulatoryfactor1anditsscaffoldingfunction AT kanemitsutakumi circadianclockcomponentperiod2regulatesdiurnalexpressionofnahexchangerregulatoryfactor1anditsscaffoldingfunction AT katamunechiharu circadianclockcomponentperiod2regulatesdiurnalexpressionofnahexchangerregulatoryfactor1anditsscaffoldingfunction AT odamasayuki circadianclockcomponentperiod2regulatesdiurnalexpressionofnahexchangerregulatoryfactor1anditsscaffoldingfunction AT kanadoyuki circadianclockcomponentperiod2regulatesdiurnalexpressionofnahexchangerregulatoryfactor1anditsscaffoldingfunction AT katomizuki circadianclockcomponentperiod2regulatesdiurnalexpressionofnahexchangerregulatoryfactor1anditsscaffoldingfunction AT moritaakari circadianclockcomponentperiod2regulatesdiurnalexpressionofnahexchangerregulatoryfactor1anditsscaffoldingfunction AT taharayu circadianclockcomponentperiod2regulatesdiurnalexpressionofnahexchangerregulatoryfactor1anditsscaffoldingfunction AT matsunaganaoya circadianclockcomponentperiod2regulatesdiurnalexpressionofnahexchangerregulatoryfactor1anditsscaffoldingfunction AT shibatashigenobu circadianclockcomponentperiod2regulatesdiurnalexpressionofnahexchangerregulatoryfactor1anditsscaffoldingfunction AT ohdoshigehiro circadianclockcomponentperiod2regulatesdiurnalexpressionofnahexchangerregulatoryfactor1anditsscaffoldingfunction |