The calcium-regulated transcription factor NFAT is emerging as a key regulator of neuronal development and plasticity but precise cellular consequences of NFAT function remain poorly understood. Here, we report that the single Drosophila NFAT homolog is widely expressed in the nervous system including motor neurons and unexpectedly controls neural excitability. Likely due to this effect on excitability, NFAT regulates overall larval locomotion and both chronic and acute forms of activity-dependent plasticity at the larval glutamatergic neuro-muscular synapse. Specifically, NFAT-dependent synaptic phenotypes include changes in the number of pre-synaptic boutons, stable modifications in synaptic microtubule architecture and pre-synaptic transmitter release, while no evidence is found for synaptic retraction or alterations in the level of the synaptic cell adhesion molecule FasII. We propose that NFAT regulates pre-synaptic development and constrains long-term plasticity by dampening neuronal excitability.
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http://dx.doi.org/10.1016/j.mcn.2010.12.010 | DOI Listing |
Front Cell Dev Biol
December 2024
MitoCare Center, Department of Pathology and Genomic Medicine, Thomas Jefferson University, Philadelphia, PA, United States.
The activation of IP receptor (IPR) Ca channels generates agonist-mediated Ca signals that are critical for the regulation of a wide range of biological processes. It is therefore surprising that CRISPR induced loss of all three IPR isoforms (TKO) in HEK293 and HeLa cell lines yields cells that can survive, grow and divide, albeit more slowly than wild-type cells. In an effort to understand the adaptive mechanisms involved, we have examined the activity of key Ca dependent transcription factors (NFAT, CREB and AP-1) and signaling pathways using luciferase-reporter assays, phosphoprotein immunoblots and whole genome transcriptomic studies.
View Article and Find Full Text PDFbioRxiv
December 2024
Walther Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians-Universität München, Goethestr.33, 80336 Munich, Germany.
T lymphocyte activation is a crucial process in the regulation of innate and adaptive immune responses. The ion channel-kinase TRPM7 has previously been implicated in cellular Mg homeostasis, proliferation, and immune cell modulation. Here, we show that pharmacological and genetic silencing of TRPM7 leads to diminished human CD4 T-cell activation and proliferation following TCR mediated stimulation.
View Article and Find Full Text PDFClin Exp Rheumatol
December 2024
Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, and Division of Allergy, Immunology & Rheumatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Objectives: Deltex1 is a transcriptional target of NFAT that promotes T cell anergy. However, whether Deltex1 affects the properties of regulatory T cells (Tregs), which are involved in the pathogenesis of Sjögren's disease (SjD), is unknown.
Methods: T cells were purified from peripheral blood using a negative selection method.
Mol Brain
November 2024
Department of Molecular Neurochemistry, Medical University of Lodz, Lodz, Poland.
Brain-derived neurotrophic factor (BDNF) is known for its potent prosurvival effect. Despite successfully replicating this effect in various clinical and pre-clinical models, the complete characterization of the molecular mechanisms underlying its neuroprotective action remains incomplete. Emerging research suggests a vital role for A-kinase anchoring proteins (AKAPs) as central nodal points orchestrating BDNF-dependent signaling.
View Article and Find Full Text PDFInt J Rheum Dis
November 2024
Department of Clinical Immunology, Xijing Hospital, and National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, Shaanxi, China.
Aim: Rheumatoid arthritis (RA) is a prevalent autoimmune disease characterized by immune dysegulation, including an immune imbalance due to abnormal activation of non-classical Th1 cells (CD161 Th1). This study investigated the effects of CCR5 on the activation and proliferation of CD161 Th1 and their pathogenicity in patients with RA.
Methods: The study was conducted on 53 patients with RA and 32 age- and sex-matched healthy controls (HC).
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