دورية أكاديمية
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G protein β subunits regulate Ca v 3.3 T-type channel activity and current kinetics via interaction with the Ca v 3.3 C-terminus.

التفاصيل البيبلوغرافية
العنوان: G protein β subunits regulate Ca v 3.3 T-type channel activity and current kinetics via interaction with the Ca v 3.3 C-terminus.
المؤلفون: Jeong S; Department of Life Science, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 04107, Republic of Korea., Lee BY; Department of Life Science, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 04107, Republic of Korea., Rhee JS; Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Synaptic Physiology Group, Hermann-Rein-Str. 3, 37075 Göttingen, Germany., Lee JH; Department of Life Science, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 04107, Republic of Korea. Electronic address: jhleem@sogang.ac.kr.
المصدر: Biochimica et biophysica acta. Biomembranes [Biochim Biophys Acta Biomembr] 2024 Aug; Vol. 1866 (6), pp. 184337. Date of Electronic Publication: 2024 May 17.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101731713 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-2642 (Electronic) Linking ISSN: 00052736 NLM ISO Abbreviation: Biochim Biophys Acta Biomembr Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Amsterdam : Elsevier
مواضيع طبية MeSH: Calcium Channels, T-Type*/metabolism , Calcium Channels, T-Type*/genetics , Calcium Channels, T-Type*/chemistry , GTP-Binding Protein beta Subunits*/metabolism , GTP-Binding Protein beta Subunits*/genetics , GTP-Binding Protein beta Subunits*/chemistry, Animals ; Humans ; Rats ; Calcium Channels, R-Type ; Cation Transport Proteins ; GTP-Binding Protein gamma Subunits/metabolism ; GTP-Binding Protein gamma Subunits/genetics ; GTP-Binding Protein gamma Subunits/chemistry ; HEK293 Cells ; Kinetics ; Patch-Clamp Techniques ; Protein Binding
مستخلص: Ca 2+ influx through Ca v 3.3 T-type channel plays crucial roles in neuronal excitability and is subject to regulation by various signaling molecules. However, our understanding of the partners of Ca v 3.3 and the related regulatory pathways remains largely limited. To address this quest, we employed the rat Ca v 3.3 C-terminus as bait in yeast-two-hybrid screenings of a cDNA library, identifying rat Gβ 2 as an interaction partner. Subsequent assays revealed that the interaction of Gβ 2 subunit was specific to the Ca v 3.3 C-terminus. Through systematic dissection of the C-terminus, we pinpointed a 22 amino acid sequence (amino acids 1789-1810) as the Gβ 2 interaction site. Coexpression studies of rat Ca v 3.3 with various Gβγ compositions were conducted in HEK-293 cells. Patch clamp recordings revealed that coexpression of Gβ 2 γ 2 reduced Ca v 3.3 current density and accelerated inactivation kinetics. Interestingly, the effects were not unique to Gβ 2 γ 2, but were mimicked by Gβ 2 alone as well as other Gβγ dimers, with similar potencies. Deletion of the Gβ 2 interaction site abolished the effects of Gβ 2 γ 2 . Importantly, these Gβ 2 effects were reproduced in human Ca v 3.3. Overall, our findings provide evidence that Gβ(γ) complexes inhibit Ca v 3.3 channel activity and accelerate the inactivation kinetics through the Gβ interaction with the Ca v 3.3 C-terminus.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: Ca(v)3.3 T-type Ca(2+) channel; G protein βγ subunits; Gating current; Whole cell patch clamp recording; Yeast-two hybrid
المشرفين على المادة: 0 (CACNA1E protein, human)
0 (Calcium Channels, R-Type)
0 (Calcium Channels, T-Type)
0 (Cation Transport Proteins)
0 (GTP-Binding Protein beta Subunits)
0 (GTP-Binding Protein gamma Subunits)
0 (CACNA1I protein, human)
تواريخ الأحداث: Date Created: 20240519 Date Completed: 20240613 Latest Revision: 20240627
رمز التحديث: 20240627
DOI: 10.1016/j.bbamem.2024.184337
PMID: 38763272
قاعدة البيانات: MEDLINE
الوصف
تدمد:1879-2642
DOI:10.1016/j.bbamem.2024.184337