TWIK-Related K channels (TREK), including TREK-1 and TREK-2, belong to the TREK/TRAAK subclass of two-pore domain K (K2P) family. The important functions of transmembrane segment 4 (M4)-glycine hinge in TREK channel gating have been characterized, but the roles of M2-hinge (the equivalent residue of M4-hinge) remain unclear. Here, by characterizing the macroscopic currents, subcellular localization and gating properties of their M2-hinge mutants (G166A for TREK-1 and G196A for TREK-2), we investigated the functions of M2-hinge. G166A displayed decreased whole-cell currents, whereas no current was produced by G196A. Subcellular analysis indicated that both mutants were aggregated near the perinuclear region, and most of them were retented within the endoplasmic reticulum (ER). Next, to explore the roles of M2-hinge in the gating mechanism, we tested the responses of the related M2-hinge mutants to 2-Aminoethoxydiphenyl borate (2-APB) and extracellular pH alteration (ΔpH). TREK-1mut7-G166A displayed reduced sensitivity to 2-APB activation, but similar sensitivity to ΔpH, when compared with TREK-1mut7. WT-ΔpCt, a TREK-2 tandom dimer, was used to assess the function of M2-hinge in the cis-type gating of TREK-2. The sensitivities of G196A-ΔpCt to both 2-APB and ΔpH decreased compared with WT-ΔpCt. Taken together, our results reveal that the M2-hinge of TREK channels control their macroscopic current, subcellular localization and gating process.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bbrc.2017.06.200 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Amiloride sensitizes prostate cancer cells to the reversible tyrosine kinase inhibitor lapatinib by modulating Erbb3 subcellular localization.
Cell Mol Life Sci
December 2024
Research Service, VA Northern California Health Care System, Mather, CA, USA.
Neoadjuvant therapy (NAT) has been studied in clinically localized prostate cancer (PCa) to improve the outcomes from radical prostatectomy (RP) by 'debulking' of high-risk PCa; however, using androgen deprivation therapy (ADT) at this point risks castration resistant PCa (CRPC) clonal proliferation. Our goal is to identify alternative NAT that reduce hormone sensitive PCa (HSPC) without affecting androgen receptor (AR) transcriptional activity. PCa is associated with increased expression and activation of the epidermal growth factor receptor (EGFR) family, including HER2 and ErbB3.
View Article and Find Full Text PDFA soluble TLR5 is involved in the flagellin-MyD88-mediated immune response via regulation rather than activation in large yellow croaker (Larimichthys crocea).
Comp Biochem Physiol B Biochem Mol Biol
December 2024
State Key Laboratory of Mariculture Breeding, Fisheries College, Jimei University, Xiamen 361021, China. Electronic address:
Toll-like receptor 5 (TLR5) plays a crucial role in the immune response through recognizing bacterial flagellin. Some teleosts possess two forms of TLR5, including a canonical membrane TLR5 (TLR5M) ortholog and a piscine soluble TLR5 (TLR5S). In this report, the full-length cDNA sequences of Larimichthys crocea TLR5M (LcTLR5M) and TLR5S (LcTLR5S) were identified.
View Article and Find Full Text PDFAlleviation of cadmium toxicity and minimizing its accumulation in rice plants by methyl jasmonate: performance and mechanisms.
J Biotechnol
December 2024
School of Environmental Science and Engineering, Shaanxi University of Science & Technology, Xi'an 710021, PR China.
Heavy metal pollution is a worldwide problem that threaten agricultural production and human health. Methyl jasmonate (MeJA) is a phytohormone that could enhance plant resistance against various stresses. However, the mechanism of MeJA in cadmium (Cd) uptake, distribution, and translocation in rice plants remains elusive.
View Article and Find Full Text PDFAKT1-Mediated NOTCH1 phosphorylation promotes gastric cancer progression via targeted regulation of IRS-1 transcription.
J Cancer Res Clin Oncol
December 2024
The First Clinical Medical College, Lanzhou University, Lanzhou, 730000, China.
Purpose: This study aimed to investigate that AKT1-Mediated NOTCH1 phosphorylation promotes gastric cancer (GC) progression via targeted regulation of IRS-1 transcription.
Methods: The study utilized databases such as PhosphositePlus, TRANSFAC, CHEA, GPS 5.0, and TCGA, along with experimental techniques including Western Blot, co-IP, in vitro kinase assay, construction of lentiviral overexpression and silencing vectors, immunoprecipitation, modified proteomics, immunofluorescence, ChIP-PCR, EdU assay, Transwell assay, and scratch assay to investigate the effects of AKT1-induced Notch1 phosphorylation on cell proliferation, invasion and migration in vitro, as well as growth and epithelial-mesenchymal transition (EMT) in vivo.
BiGM-lncLoc: Bi-level Multi-Graph Meta-Learning for Predicting Cell-Specific Long Noncoding RNAs Subcellular Localization.
Interdiscip Sci
December 2024
School of Information, Yunnan Normal University, Kunming, 650500, China.
The precise spatiotemporal expression of long noncoding RNAs (lncRNAs) plays a pivotal role in biological regulation, and aberrant expression of lncRNAs in different subcellular localizations has been intricately linked to the onset and progression of a variety of cancers. Computational methods provide effective means for predicting lncRNA subcellular localization, but current studies either ignore cell line and tissue specificity or the correlation and shared information among cell lines. In this study, we propose a novel approach, BiGM-lncLoc, treating the prediction of lncRNA subcellular localization across cell lines as a multi-graph meta-learning task.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!