Cytolytic CD8(+) T cells (CTLs) kill virally infected cells, tumor cells, or other potentially autoreactive T cells in a calcium-dependent manner. To date, the molecular mechanism that leads to calcium intake during CTL differentiation and function has remained unresolved. We demonstrate that desmoyokin (AHNAK1) is expressed in mature CTLs, but not in naive CD8(+) T cells, and is critical for calcium entry required for their proper function during immune response. We show that mature AHNAK1-deficient CTLs exhibit reduced Ca(v)1.1 alpha1 subunit expression (also referred to as L-type calcium channels or alpha1S pore-forming subunits), which recently were suggested to play a role in calcium entry into CD4(+) T cells. AHNAK1-deficient CTLs show marked reduction in granzyme-B production, cytolytic activity, and IFN-gamma secretion after T cell receptor stimulation. Our results demonstrate an AHNAK1-dependent mechanism controlling calcium entry during CTL effector function.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701053 | PMC |
| http://dx.doi.org/10.1073/pnas.0902844106 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Familial Alzheimer's disease mutations in amyloid precursor protein impair calcineurin signaling to NMDA receptors.
J Biol Chem
December 2024
Department of Pharmacology, Addiction Science, and Toxicology, College of Medicine, The University of Tennessee Health Science Center; Memphis, 38163. Electronic address:
Familial Alzheimer's disease (FAD) is frequently associated with mutations in the amyloid precursor protein (APP), which are thought to lead to cognitive deficits by impairing NMDA receptor (NMDAR)-dependent forms of synaptic plasticity. Given the reliance of synaptic plasticity on NMDAR-mediated Ca entry, shaping of NMDAR activity by APP and/or its disease-causing variants could provide a basis for understanding synaptic plasticity impairments associated with FAD. A region of APP (residues 639-644 within APP695) processed by the γ-secretase complex, which generates amyloid β (Aβ) peptides, is a hotspot for FAD mutations.
View Article and Find Full Text PDFEldecalcitol alleviates diabetic periodontitis by regulating macrophage efferocytosis and polarization via SOCE machinery.
Int Immunopharmacol
December 2024
Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No.44-1 Wenhua Road West, 250012, Jinan, Shandong, China; Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, China; School of Clinical Medicine, Jining Medical University, Jining, China; Institute of Oral Basic Research, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University. Electronic address:
Diabetes exacerbates the occurrence and severity of periodontitis, the pathogenesis of diabetic periodontitis (DPD) is influenced by the delayed resolution of inflammation. Eldecalcitol (ED-71) has shown promise in preventing bone loss in DPD. We herein aimed to investigate the role of ED-71 in the inflammatory regression phase of DPD and elucidate the underlying mechanisms.
View Article and Find Full Text PDFReduced voltage-activated Ca2+ release flux in muscle fibers from a rat model of Duchenne dystrophy.
J Gen Physiol
March 2025
University Lyon, Université Claude Bernard Lyon 1, CNRS UMR-5261, INSERM U-1315, Institut NeuroMyoGène - Pathophysiology and Genetics of Neuron and Muscle , Lyon, France.
The potential pathogenic role of disturbed Ca2+ homeostasis in Duchenne muscular dystrophy (DMD) remains a complex, unsettled issue. We used muscle fibers isolated from 3-mo-old DMDmdx rats to further investigate the case. Most DMDmdx fibers exhibited no sign of trophic or morphology distinction as compared with WT fibers and mitochondria and t-tubule membrane networks also showed no stringent discrepancy.
View Article and Find Full Text PDFWide-ranging cellular functions of ion channels and lipid scramblases in the structurally related TMC, TMEM16 and TMEM63 families.
Nat Struct Mol Biol
December 2024
Department of Physiology, University of California, San Francisco, San Francisco, CA, USA.
Calcium (Ca)-activated ion channels and lipid scramblases in the transmembrane protein 16 (TMEM16) family are structurally related to mechanosensitive ion channels in the TMEM63 and transmembrane channel-like (TMC) families. Members of this structurally related superfamily share similarities in gating transitions and serve a wide range of physiological functions, which is evident from their disease associations. The TMEM16, TMEM63 and TMC families include members with important functions in the cell membrane and/or intracellular organelles such as the endoplasmic reticulum, membrane contact sites, endosomes and lysosomes.
View Article and Find Full Text PDFCalmodulin binding is required for calcium mediated TRPA1 desensitization.
bioRxiv
December 2024
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA.
Calcium (Ca) ions affect nearly all aspects of biology. Excessive Ca entry is cytotoxic and Ca-mobilizing receptors have evolved diverse mechanisms for tight regulation that often include Calmodulin (CaM). TRPA1, an essential Ca-permeable ion channel involved in pain signaling and inflammation, exhibits complex Ca regulation with initial channel potentiation followed by rapid desensitization.
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!