Calcium (Ca2+) signals regulate a diverse set of cellular responses, from proliferation to muscular contraction and neuro-endocrine secretion. The ubiquitous Ca2+ sensor, calmodulin (CaM), translates changes in local intracellular Ca2+ concentrations into changes in enzyme activities. Among its targets, the Ca2+/CaM-dependent protein kinases I and IV (CaMKs) are capable of transducing intraneuronal signals, and these kinases are implicated in neuronal gene regulation that mediates synaptic plasticity in mammals. Recently, the cyclic AMP response element binding protein (CREB) has been proposed as a target for a CaMK cascade involving not only CaMKI or CaMKIV, but also an upstream kinase kinase that is also CaM regulated (CaMKK). Here, we report that all components of this pathway are coexpressed in head neurons of Caenorhabditis elegans. Utilizing a transgenic approach to visualize CREB-dependent transcription in vivo, we show that this CaMK cascade regulates CRE-mediated transcription in a subset of head neurons in living nematodes.
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http://dx.doi.org/10.1093/embo-reports/kvf191 | DOI Listing |
Cell Commun Signal
January 2025
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Road II, Shanghai, 200025, China.
Receptor activator of nuclear factor kappa-B ligand (RANKL) initiates a complex signaling cascade that is crucial for inducing osteoclast differentiation and activation. RANKL-induced signaling has been analyzed in detail, and the involvement of TNF receptor-associated factor 6 (TRAF6), calmodulin-dependent protein kinase (CaMK), NF-κB, mitogen-activated protein kinase (MAPK), activator protein-1 (AP-1), and molecules that contain an immunoreceptor tyrosine-based activation motif (ITAM) has been reported. However, the precise molecular steps that regulate RANKL signaling remain largely unknown.
View Article and Find Full Text PDFJ Neurochem
January 2025
Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Misfolding and accumulation of amyloid-β (Aβ) in the brains of patients with Alzheimer's disease (AD) lead to neuronal loss through various mechanisms, including the downregulation of eukaryotic elongation factor 2 (EEF2) protein synthesis signaling. This study investigated the neuroprotective effects of indole and coumarin derivatives on Aβ folding and EEF2 signaling using SH-SY5Y cells expressing Aβ-green fluorescent protein (GFP) folding reporter. Among the tested compounds, two indole (NC009-1, -6) and two coumarin (LM-021, -036) derivatives effectively reduced Aβ misfolding and associated reactive oxygen species (ROS) production.
View Article and Find Full Text PDFSci Rep
November 2024
Key laboratory of molecular pathology in Tumors of Guangxi Higher Education Institutions, Department of Pathology, the Affiliated Hospital of Youjiang Medical University for Nationalities, Baise City, 533000, Guangxi Zhuang Autonomous Region, China.
Eukaryotic Elongation Factor 2 Kinase (eEF2K), a member of the α-kinase family, services as a crucial negative regulator of protein synthesis, particularly under conditions of cellular stress. A pan-cancer analysis of eEF2K expression, genetic variants, and clinical relevance across multiple tumor types was performed using data from the Cancer Genome Atlas (TCGA) and GEO. Our findings suggest that eEF2K has dual roles in cancer progression, with its expression correlating with patient prognosis.
View Article and Find Full Text PDFBiochem Pharmacol
January 2025
Laboratório de Farmacologia e Neurobiologia, Instituto de Ciências Biomédicas de Abel Salazar Universidade do Porto (ICBAS-UP), 4050-313 Porto, Portugal; Centro de Investigação Farmacológica e Inovação Medicamentosa (MedInUP/RISE-Health), Instituto de Ciências Biomédicas de Abel Salazar Universidade do Porto (ICBAS-UP), 4050-313 Porto, Portugal. Electronic address:
Nicotinic α7 receptors (α7 nAChRs) present in perisynaptic Schwann cells (PSCs) control acetylcholine (ACh) spillover from the neuromuscular synapse by transiently increasing intracellular Ca, which fosters adenosine release via type 1 equilibrative nucleoside transporters (ENT1) and retrograde activation of presynaptic A inhibitory receptors. The putative Ca-dependent pathways downstream α7 nAChRs involved in the sensing inhibitory drive operated by PSCs is unknown. Herein, we used phrenic nerve-hemidiaphragm preparations from Wistar rats.
View Article and Find Full Text PDFJ Neurosci
November 2024
Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045.
The cAMP-response element binding protein (CREB) transcription factor controls the expression of the neuronal immediate early genes , , and and is essential for long-lasting synaptic plasticity underlying learning and memory. Despite this critical role, there is still ongoing debate regarding the synaptic excitation-transcription (E-T) coupling mechanisms mediating CREB activation in the nucleus. Here we employed optical uncaging of glutamate to mimic synaptic excitation of distal dendrites in conjunction with simultaneous imaging of intracellular Ca dynamics and transcriptional reporter gene expression to elucidate CREB E-T coupling mechanisms in hippocampal neurons cultured from both male and female rats.
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