Ask about this productRelated genes to: LRRC26 Blocking Peptide
- Gene:
- LRRC26 NIH gene
- Name:
- leucine rich repeat containing 26
- Previous symbol:
- -
- Synonyms:
- bA350O14.10, OTTHUMG00000020980
- Chromosome:
- 9q34.3
- Locus Type:
- gene with protein product
- Date approved:
- 2004-06-02
- Date modifiied:
- 2015-08-25
Related products to: LRRC26 Blocking Peptide
Related articles to: LRRC26 Blocking Peptide
- Big-conductance, Ca²-activated K (BK) channels consist of Ca²- and voltage-sensing, pore-forming α (BKα) subunits and regulatory auxiliary β or γ subunits. Concatenated subunit constructs are powerful tools for elucidating subunit stoichiometry in ion channel gating and regulation, allowing control over subunit arrangement, stoichiometry, and mutation. However, the additional S0 transmembrane segment in BKα places its N- and C-termini on opposite sides of the membrane, preventing tandem BK channel subunit construction by conventional methods. To investigate the atypical 'all-or-none' modulatory function of γ subunits and the subunit stoichiometry of BK channel gating, we developed concatenated constructs containing 2 or 4 BKα subunits by splicing them into modular forms that can be co-expressed to form functional channels. These constructs retained voltage and Ca² gating properties similar to intact BK channels. By fusing the LRRC26 (γ1) subunit to the N-terminus of tandem BKα constructs, we found that a single γ1 subunit per α subunit tetramer is sufficient to fully modulate the channel. Furthermore, the L312A mutation in the deep pore region exhibited a stoichiometrically graded effect on voltage-gated BK channel activation. In contrast, a V288A mutation at the selectivity filter induced channel inactivation only when present in all four BKα subunits. Thus, by engineering concatenated BKα constructs, we identified three distinct stoichiometric modes of BK channel gating control by LRRC26, the pore, and the selectivity filter. This study offers new molecular tools and advances our understanding of subunit stoichiometry in BK channel gating and modulation. - Source: PubMed
Publication date: 2026/03/05
Chen GuanxingLi QinShah KunalYan Jiusheng - Association of auxiliary subunits (β1-4 and γ1-4) with the pore-forming α subunit of the calcium- and voltage-activated potassium (BK) channel provides functional diversity. γ1 promotes a significant leftward shift in the voltage-activation curve, ensuring proper function of secretory glands and allowing BK channels to release K at the cell's resting Ca concentration. Given its physiological importance, it is crucial to elucidate the mechanisms of γ1 action. However, structural and functional studies have yielded conflicting conclusions regarding the modulation of BK channels by γ1. Here, using macroscopic, single-channel, and gating-current measurements, we demonstrate that at zero mV, γ1 increases 106-fold the equilibrium constant for the closed-open transition by destabilizing the channel's closed state and enhancing coupling between the voltage sensor and the pore domain, without affecting voltage-sensor activation. These results suggest that γ1 not only increases the energetic coupling between the voltage sensors and the pore but also primarily enhances the channel-opening reaction. - Source: PubMed
Publication date: 2026/02/17
Echeverría FelipePeña-Pichicoi AntonioFernandez MiguelCarrasquel-Ursulaez WillyCastillo Juan PAlvarez OsvaldoLatorre Ramon - The retinoid X receptor (RXR) is a ligand-activated nuclear receptor that heterodimerizes with numerous partners to regulate diverse transcriptional programs. RXR agonists, including the FDA-approved drug bexarotene, show anti-tumor activity but are limited by adverse side effects. V-125 is a next-generation RXR agonist engineered for improved selectivity, pharmacokinetics, and reduced lipogenic effects. This study compares the molecular and functional effects of V-125 and bexarotene in HER2 breast cancer models. Female MMTV-Neu mice bearing mammary tumors were treated with control, V-125 (100 mg/kg diet), or bexarotene (100 mg/kg diet) for 10 days. RNA sequencing was used to identify differentially expressed genes and pathways. Candidate targets were validated by qPCR and immunohistochemistry (IHC). Immune modulation was evaluated by IHC staining for CD8 cells and CD206 macrophages in tumors to capture the tumor microenvironment. Functional assays in JIMT-1 human HER2 cells assessed RXR target activation and clonogenic potential in tumor cells. V-125 induced broader transcriptional changes than bexarotene, including selective upregulation of , , , and genes associated with improved patient survival. Pathway analysis revealed regulation of immune activation, cancer signaling, and lipid metabolism. Both V-125 and bexarotene suppressed colony formation in JIMT-1 cells, confirming previous observations about RXR-dependent inhibition of tumor cell growth. Moreover, V-125 in vivo had distinct capabilities to increase CD8 cell infiltration and reduced CD206 macrophages, whereas bexarotene did not. V-125 but not bexarotene reprograms tumor transcriptional programs and the immune landscape in an anti-tumor manner in the MMTV-neu mouse model and in in vitro models of HER2 breast cancer. This highlights its promise as a selective RXR agonist with anti-tumor and immunomodulatory activity in HER2 breast cancer. - Source: PubMed
Publication date: 2025/12/30
Chowdhury Afrin SultanaReich Lyndsey ALiby Karen TYeh Elizabeth SLeal Ana S - Association of auxiliary subunits ( and ) with the pore-forming subunit of the calcium-and voltage-activated potassium (BK) channel provides functional diversity. promotes a significant leftward shift of the voltage activation curve, ensuring the adequate functioning of secretory glands, allowing the BK channel to release at the cell's resting concentration. Given its physiological importance, it is crucial to elucidate the mechanisms of action. However, structural and functional studies have yielded conflicting conclusions regarding the modulation of BK channels by . Here, using macroscopic, single-channel, and gating current measurements, we demonstrate that at zero mV increases 92-fold the equilibrium constant that defines the closed-open transition by destabilizing the channel's closed configuration and enhancing the coupling between the voltage sensor and the pore domain, without affecting voltage-sensor activation. These results suggest that not only causes an increase in the energetic coupling between the voltage sensors and the pore but mainly enhances the channel opening reaction. - Source: PubMed
Publication date: 2025/09/06
Echeverria FelipePeña-Pichicoi AntonioFernandez MiguelCarrasquel-Ursulaez WillyCastillo Juan PAlvarez OsvaldoLatorre Ramon - Cigarette smoke (CS) is a leading cause of chronic obstructive pulmonary disease (COPD). Here, we investigated whether the ion channel amplifier nesolicaftor rescues CS-induced mucociliary and ion channel dysfunction. As CS increases the expression of transforming growth factor-beta1 (TGF-β1), human bronchial epithelial cells (HBECs) from healthy donors were used for TGF-β1 and COPD donors (COPD-HBEC) for CS exposure experiments. CS and TGF-β1 induce mucociliary dysfunction by increasing MUC5AC and decreasing ion channel conductance important for mucus hydration. These include cystic fibrosis transmembrane conductance regulator (CFTR) and apical large-conductance, Ca-activated K (BK) channels. Nesolicaftor rescued CFTR and BK channel dysfunction, restored ciliary beat frequency (CBF), and decreased mucus viscosity and MUC5AC expression in CS-exposed COPD-HBEC. Nesolicaftor further reversed reductions in airway surface liquid (ASL) volumes, CBF, and CFTR and BK conductance, and blocked the increase in extracellular signal-regulated kinase (ERK) signaling in TGF-β1-exposed normal HBECs. Mechanistically, nesolicaftor increased, as expected, not only binding of PCBP1 to mRNA but also surprisingly to mRNA, which encodes the gamma subunit required for BK function. Similar to nesolicaftor, the angiotensin receptor blocker (ARB) losartan rescued TGF-β1-mediated decreases in PCBP1 binding to mRNA. In addition, the ARB telmisartan restored PCBP1 binding to and mRNAs to rescue CFTR and BK function in CS-exposed COPD-HBEC. Thus, nesolicaftor and ARBs act on the same target and were therefore neither additive nor synergistic in their actions. These data demonstrate that nesolicaftor and ARBs may provide benefits in COPD by improving ion channel function important for mucus hydration. Cigarette smoke (CS) increases transforming growth factor-beta1 (TGF-β1) expression that causes mucociliary dysfunction by decreasing ion channel function. In our study, a CFTR amplifier (nesolicaftor) and angiotensin II receptor blockers (losartan and telmisartan) improve CS-induced ion channel dysfunction, by increasing binding of PCBP1 to and mRNAs. Therefore, nesolicaftor and ARBs, acting on the same target, may provide therapeutic benefits for treating smoking-related diseases. - Source: PubMed
Publication date: 2025/03/17
Silswal NeerupmaBaumlin NathalieHaworth StevenMontgomery Robert NYoshida MakotoDennis John SYerrathota SireeshaKim Michael DSalathe Matthias