Circadian clock component PERIOD2 regulates diurnal expression of Na+/H+ exchanger regulatory factor-1 and its scaffolding function

Autor:	Shigenobu Shibata, Yu Tahara, Satoru Koyanagi, Mizuki Kato, Chiharu Katamune, Shigehiro Ohdo, Yuya Tsurudome, Yuki Kanado, Masayuki Oda, Naoya Matsunaga, Akari Morita, Takumi Kanemitsu
Jazyk:	angličtina
Rok vydání:	2018
Předmět:	0301 basic medicine chemistry.chemical_classification Regulation of gene expression Scaffold protein Multidisciplinary Immunoprecipitation Liver cytology Circadian clock lcsh:R Fatty acid lcsh:Medicine Cell biology PER2 03 medical and health sciences Transactivation 030104 developmental biology chemistry lcsh:Q lcsh:Science
Zdroj:	Scientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)
ISSN:	2045-2322
DOI:	10.1038/s41598-018-27280-w
Popis:	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.
Databáze:	OpenAIRE
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