دورية أكاديمية
أعرض في EDS

The β 4 subunit of the voltage-gated calcium channel (Cacnb4) regulates the rate of cell proliferation in Chinese Hamster Ovary cells.

التفاصيل البيبلوغرافية
العنوان: The β 4 subunit of the voltage-gated calcium channel (Cacnb4) regulates the rate of cell proliferation in Chinese Hamster Ovary cells.
المؤلفون: Rima M; INSERM UMR1087, LabEx Ion Channels Science and Therapeutics, Institut du Thorax, Nantes, F-44000 France; CNRS, UMR6291, Nantes, F-44000 France; Azm Center for Research in Biotechnology and its Application, Lebanese University, 1300, Tripoli, Lebanon., Daghsni M; INSERM UMR1087, LabEx Ion Channels Science and Therapeutics, Institut du Thorax, Nantes, F-44000 France; CNRS, UMR6291, Nantes, F-44000 France; Université de Tunis El Manar, Faculté de Médecine de Tunis, LR99ES10 Laboratoire de Génétique Humaine, 1007, Tunis, Tunisia., De Waard S; INSERM UMR1087, LabEx Ion Channels Science and Therapeutics, Institut du Thorax, Nantes, F-44000 France; CNRS, UMR6291, Nantes, F-44000 France; Université de Nantes, Nantes, F-44000 France., Gaborit N; INSERM UMR1087, LabEx Ion Channels Science and Therapeutics, Institut du Thorax, Nantes, F-44000 France; CNRS, UMR6291, Nantes, F-44000 France; Université de Nantes, Nantes, F-44000 France., Fajloun Z; Azm Center for Research in Biotechnology and its Application, Lebanese University, 1300, Tripoli, Lebanon; Faculty of Sciences III, Lebanese University, 1300, Tripoli, Lebanon., Ronjat M; INSERM UMR1087, LabEx Ion Channels Science and Therapeutics, Institut du Thorax, Nantes, F-44000 France; CNRS, UMR6291, Nantes, F-44000 France; Université de Nantes, Nantes, F-44000 France., Mori Y; Laboratory of Molecular Biology, Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyoto, Japan., Brusés JL; Department of Natural Sciences, Mercy College, Dobbs Ferry, NY 10522, USA., De Waard M; INSERM UMR1087, LabEx Ion Channels Science and Therapeutics, Institut du Thorax, Nantes, F-44000 France; CNRS, UMR6291, Nantes, F-44000 France; Université de Nantes, Nantes, F-44000 France. Electronic address: michel.dewaard@univ-nantes.fr.
المصدر: The international journal of biochemistry & cell biology [Int J Biochem Cell Biol] 2017 Aug; Vol. 89, pp. 57-70. Date of Electronic Publication: 2017 Jun 03.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 9508482 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-5875 (Electronic) Linking ISSN: 13572725 NLM ISO Abbreviation: Int J Biochem Cell Biol Subsets: MEDLINE
أسماء مطبوعة: Publication: Amsterdam : Elsevier
Original Publication: Exeter, England ; Tarrytown, NY, U.S.A. : Pergamon, c1995-
مواضيع طبية MeSH: Calcium Channels/*metabolism, Animals ; CHO Cells ; Calcium Channels/genetics ; Cell Cycle ; Cell Nucleolus/metabolism ; Cell Proliferation ; Cricetinae ; Cricetulus ; Gene Expression Regulation ; Mice ; Mutation ; Protein Transport
مستخلص: The β subunits of Voltage-Gated Calcium Channel (VGCC) are cytosolic proteins that interact with the VGCC pore -forming subunit and participate in the trafficking of the channel to the cell membrane and in ion influx regulation. β subunits also exert functions independently of their binding to VGCC by translocation to the cell nucleus including the control of gene expression. Mutations of the neuronal Cacnb4 (β 4 ) subunit are linked to human neuropsychiatric disorders including epilepsy and intellectual disabilities. It is believed that the pathogenic phenotype induced by these mutations is associated with channel-independent functions of the β 4 subunit. In this report, we investigated the role of β 4 subunit in cell proliferation and cell cycle progression and examined whether these functions could be altered by a pathogenic mutation. To this end, stably transfected Chinese Hamster Ovary (CHO-K1) cells expressing either rat full-length β 4 or the rat C-terminally truncated epileptic mutant variant β 1-481 were generated. The subcellular localization of both proteins differed significantly. Full-length β 4 localizes almost exclusively in the cell nucleus and concentrates into the nucleolar compartment, while the C-terminal-truncated β 1-481 subunit was less concentrated within the nucleus and absent from the nucleoli. Cell proliferation was found to be reduced by the expression of β 4 , while it was unaffected by the epileptic mutant. Also, full-length β 4 interfered with cell cycle progression by presumably preventing cells from entering the S-phase via a mechanism that partially involves endogenous B56δ, a regulatory subunit of the phosphatase 2A (PP2A) that binds β 4 but not β 1-481 . Analysis of β 4 subcellular distribution during the cell cycle revealed that the protein is highly expressed in the nucleus at the G1/S transition phase and that it is translocated out of the nucleus during chromatin condensation and cell division. These results suggest that nuclear accumulation of β 4 at the G1/S transition phase affects the progression into S-phase resulting in a decrease in the rate of cell proliferation. Regulation of the cell cycle exit is a critical step in determining the number of neuronal precursors and neuronal differentiation suggesting that mutations of the β 4 subunit could affect neural development and formation of the mature central nervous system.
(Copyright © 2017. Published by Elsevier Ltd.)
فهرسة مساهمة: Keywords: CHO cells; Ca(v)β; Cell cycle; Cell proliferation; Epilepsy; Voltage-gated calcium channel
المشرفين على المادة: 0 (Cacnb4 protein, rat)
0 (Calcium Channels)
تواريخ الأحداث: Date Created: 20170608 Date Completed: 20171120 Latest Revision: 20180124
رمز التحديث: 20221213
DOI: 10.1016/j.biocel.2017.05.032
PMID: 28587927
قاعدة البيانات: MEDLINE
الوصف
تدمد:1878-5875
DOI:10.1016/j.biocel.2017.05.032