Ask about this productRelated genes to: TMEM63B antibody
- Gene:
- TMEM63B NIH gene
- Name:
- transmembrane protein 63B
- Previous symbol:
- C6orf110
- Synonyms:
- DKFZp434P0531, dJ421H19.2
- Chromosome:
- 6p21.1
- Locus Type:
- gene with protein product
- Date approved:
- 2003-11-25
- Date modifiied:
- 2018-11-19
Related products to: TMEM63B antibody
Related articles to: TMEM63B antibody
- Inspiration-induced mechanical stretching serves as the primary driving force for pulmonary surfactant secretion from alveolar epithelial type II (AT2) cells. However, the mechanism by which AT2 cells sense mechanical stimuli remains elusive. Here, we demonstrate that TMEM63B functions as a critical mechanosensor on the plasma membrane of AT2 cells. We find that stretch induces significant currents in AT2 cells. Using Tmem63b mice, we show that TMEM63B is expressed on the plasma membrane of AT2 cells. Deletion of TMEM63B in AT2 cells abolishes the stretch-induced currents and suppresses the secretion of pulmonary surfactant. Activation of TMEM63B causes Ca influx, lamellar body (LB) fusion, and pulmonary surfactant secretion. These processes are markedly impaired upon TMEM63B deletion. In contrast, ATP-induced Ca influx and LB fusion are unaffected by TMEM63B deletion, indicating that TMEM63B plays a specialized role in sensing mechanical stretch in the lungs. Therefore, our study establishes TMEM63B as a key mechanosensor critical for AT2 cell-mediated pulmonary surfactant secretion. - Source: PubMed
Publication date: 2026/04/29
Zhan Shi-YuTeng Xiao-YuWu DanZhu YunfengZhang Tian-ZiGuo Hong-LiTan XiaofengYang GuolinLi Gui-ZhouWang Yue-YingZhong Bi-XianDuan Gui-FangChen FengXu JieShi Yun Stone - Major depressive disorder (MDD) is a highly prevalent and disabling neuropsychiatric condition, its underlying molecular mechanisms remain incompletely understood. This study aimed to systematically characterize proteomic alterations in the prefrontal cortex associated with depression-like behaviors induced by chronic stress. Depression-like behaviors in mice were evaluated using standardized behavioral tests and confirmed by Digital Western blotting. Quantitative proteomic analysis of prefrontal cortex tissues was performed to compare chronic social defeat stress (CSDS) and control groups, identifying differentially expressed proteins (DEPs). These DEPs were subsequently subjected to bioinformatic analyses, including Gene Ontology (GO) enrichment and construction of protein-protein interaction (PPI) networks. Key DEPs were further validated by parallel reaction monitoring (PRM) and Western blotting. We found that CSDS mice displayed robust depression-like phenotypes, including decreased sucrose preference and increased immobility. Western blot analysis confirmed the dysregulation of ER stress markers, proinflammatory factors, and proteins related to synaptic plasticity. Proteomic analysis identified 95 differentially expressed proteins, with GO enrichment revealing predominant associations with gene regulation, mitochondrial, metabolic, and synaptic function. PPI network analysis highlighted hub proteins involved in mitochondrial, endoplasmic reticulum, and synaptic regulation. PRM and Western blot validation confirmed dysregulation in four functional modules: 1) Mitochondrial function (Mrpl17, Mrpl41)；2) Signal transduction (Rigi, Pbrm1, Plppr5, Glyr1)；3) Metabolic regulation(Pmvk, Rpl13a, Ubtd2, Tmem63b)；4) Synaptic plasticity (Kif21b, Klc4, Lama2, Col4a2). Our results demonstrate that chronic stress disrupts prefrontal cortical pathways that govern gene regulation, mitochondrial metabolism, and synaptic function, suggesting their concerted contribution to the pathophysiology of depression. - Source: PubMed
Publication date: 2026/02/27
Zhang YiLi LeiZhang XiaoweiXu JiyiKan WeijingWang TianyiDu Jing - The blood-brain barrier (BBB) plays a central role in maintaining the ionic milieu required for neuronal activity and in translating neuronal activity in a local elevation in cerebral blood flow (CBF). However, the molecular repertoire of the human BBB remains poorly defined. Here, we performed a systematic transcriptomic analysis of 672 genes using eight independent RNA-Seq datasets generated from the human brain endothelial cell line hCMEC/D3, the most widely used model of the human BBB. We focused on ion channels, ion transporters, G protein-coupled receptors (GPCRs), and Receptor Tyrosine Kinases (RTKs), which govern ionic homeostasis, barrier integrity, and CBF. Among the most abundantly expressed ion transporters were subunits of the mitochondrial F-type ATPase complex (F-type ATPase α subunit, F-type ATPase β subunit, F-type ATPase C subunit), reflecting the high metabolic demands of the BBB. Key regulators of intracellular Ca homeostasis, including SERCA2, PMCA1/4, and SPCA1, were consistently detected, supporting efficient Ca clearance across endoplasmic reticulum (ER), plasma membrane, and Golgi compartments. Our analysis of ion channels revealed a selective repertoire with prominent expression of Cl-permeable channels (CLIC1/4, CLNS1A, VDAC1-3, VRAC) and various K-permeable channels, including IK/K3.1, K2.1, K1.2, BK, K4.1, and TREK-1. Na-permeable channels (ENaC and NALCN), non-selective cation channels (TRP, HCN2/3), and ER- (InsPRs, TRICs, and putative leak channels), and lysosomes-associated (TRPML1 and TPCs) channels were also detected. Additionally, we identified transcripts for mechanosensitive channels (PIEZO1, TACAN, TMC7, TMEM63B) and gap junction proteins (Cx43, Cx45, Cx47), as well as a broad array of ionotropic and metabotropic receptors, including purinergic, adenosine, histamine, GABA, adrenergic and nicotinic receptors. Growth factor-related RTKs (FGFR, IGFR, EGFR, PDGFR, VEGFR) were consistently expressed, underscoring their role in angiogenesis, endothelial-pericyte interactions, and BBB integrity. This meta-analysis highlights the conserved expression of transporter genes across datasets, contrasted with lower and more variable expression of ion channels and receptors, suggesting that the latter may be context-dependent and dynamically regulated. These findings provide a reference framework for understanding the human BBB transportome, offering new insights into the molecular toolkit of the human BBB to support future investigations into the role of endothelial ion transport in neurological disorders. - Source: PubMed
Publication date: 2025/12/18
Scarpellino GiorgiaBrunetti ValentinaScolari FrancescaVisentin LucaBiella Gerardo RosarioRuffinatti Federico AlessandroMoccia Francesco - The proper function of the lower urinary tract depends on its ability to sense and react to mechanical forces as urine is produced, transported, stored, and eliminated; however, our current understanding of the mechanosensors involved in these events is limited. TMEM63 ion channels are reported to function as mechanosensors/osmosensors in other organs, and our studies revealed that the primary site of Tmem63a and Tmem63b gene expression and TMEM63B protein expression in the mouse bladder wall was the urothelium. Despite this localization, voiding behavior in conditional urothelial Tmem63b knockout mice, assessed using a video-monitored void-spot screening assay, was not significantly different from control mice, even when the urothelium was stressed by exposure to cyclophosphamide. We further observed that dorsal root ganglia sensory neurons, including those innervating the bladder, were also sites of Tmem63a, Tmem63b, and TMEM63B expression. Again, voiding behavior was not impacted in conditional sensory neuron Tmem63b knockout mice, treated or not with cyclophosphamide. Our studies reveal that the urothelium and dorsal root ganglia are sites of Tmem63a, Tmem63b, and TMEM63B expression, but deletion of Tmem63b alone in these tissues does not result in a demonstrable voiding phenotype. - Source: PubMed
Publication date: 2025/12/05
Dalghi Marianela GRuiz Wily GClayton Dennis RParakala-Jain TanmayCarattino Marcelo DShi Yun StoneApodaca Gerard - Peripheral somatosensory neurons in the dorsal root ganglia (DRG) transduce mechanical force in the skin and other organs into electrical signals using specialized mechanically activated (MA) ion channels that initiate neuronal activation in response to force. Increasing evidence highlights PIEZO2 as the primary transducer of low-threshold mechanical force in DRG neurons. However, in the absence of Piezo2, mice and humans still respond to noxious painful stimuli like pinch, suggesting that additional MA channel(s) likely exist in DRG neurons. Developing strategies to identify Cre lines and DRG subpopulations that select for non-PIEZO2-expressing neurons is therefore an ongoing effort in the field to discover unknown mechanosensors. Here, we investigated a Vglut3-labeled mouse line as a candidate to identify non-PIEZO2 MA channels in a subtype of DRG neurons called C-fiber low-threshold mechanoreceptors (C-LTMRs). Our study carefully demonstrates that the Vglut3-IRES-Cre mouse line specifically and efficiently labels C-LTMR neurons of the DRG. Electrophysiological recordings using two different in vitro mechanical stimulation assays show that the genetically labeled Vglut3 neurons have robust indentation- and stretch-activated MA currents that are exclusively slowly or ultra-slowly adapting. To determine whether the Vglut3-IRES-Cre mouse line can be used to delete genes of interest and identify the underlying MA ion channels in C-LTMRs, we attempted to generate a Tmem63b conditional knockout using this Cre line but detected incomplete loss of Tmem63b transcript and lack of TMEM63B-dependent effect on C-LTMR MA currents. Together, our results emphasize that although the Vglut3-IRES-Cre line is robust in driving expression of a conditional reporter gene, it is inefficient in deleting genes like Tmem63b as well as Piezo2. - Source: PubMed
Publication date: 2025/11/01
Orlin Daniel JMuñoz AntonioBerryman SageSemidey DestineeMurthy Swetha E