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Minimal presynaptic protein machinery governing diverse kinetics of calcium-evoked neurotransmitter release.
Nat Commun
December 2024
Nanobiology Institute, Yale University, West Haven, CT, USA.
Neurotransmitters are released from synaptic vesicles with remarkable precision in response to presynaptic calcium influx but exhibit significant heterogeneity in exocytosis timing and efficacy based on the recent history of activity. This heterogeneity is critical for information transfer in the brain, yet its molecular basis remains poorly understood. Here, we employ a biochemically-defined fusion assay under physiologically relevant conditions to delineate the minimal protein machinery sufficient to account for various modes of calcium-triggered vesicle fusion dynamics.
View Article and Find Full Text PDFThe mechanism of discriminative aminoacylation by isoleucyl-tRNA synthetase based on wobble nucleotide recognition.
Nat Commun
December 2024
State Key Laboratory of Anti-Infective Drug Discovery and Development, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
The faithful charging of amino acids to cognate tRNAs by aminoacyl-tRNA synthetases (AARSs) determines the fidelity of protein translation. Isoleucyl-tRNA synthetase (IleRS) distinguishes tRNA from tRNA solely based on the nucleotide at wobble position (N34), and a single substitution at N34 could exchange the aminoacylation specificity between two tRNAs. Here, we report the structural and biochemical mechanism of N34 recognition-based tRNA discrimination by Saccharomyces cerevisiae IleRS (ScIleRS).
View Article and Find Full Text PDFBLOC1S1 Control of Vacuolar Organelle Fidelity Modulates Murine T2 Cell Immunity and Allergy Susceptibility.
Allergy
December 2024
Laboratory of Mitochondrial Biology and Metabolism, NHLBI, NIH, Bethesda, Maryland, USA.
Background: The levels of biogenesis of lysosome organelles complex 1 subunit 1 (BLOC1S1) control mitochondrial and endolysosome organelle homeostasis and function. Reduced fidelity of these vacuolar organelles is increasingly being recognized as important in instigating cell-autonomous immune cell activation. We reasoned that exploring the role of BLOC1S1 in CD4 T cells may further advance our understanding of regulatory events linked to mitochondrial and/or endolysosomal function in adaptive immunity.
View Article and Find Full Text PDFRe-scoping ultradian rhythms in the context of metabolism.
Front Physiol
December 2024
Energy and Sustainability Research Institute Groningen, Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, Netherlands.
Rapid, ultradian biological rhythms are only partly comparable to circadian (24-h) rhythms. Often, the ensuing expectations from this comparison are that 1) ultradian rhythms should be driven by discrete oscillators, 2) they are biochemically buffered, and 3) they must be functionally linked to extrinsic events and cycles. These three expectations are not always met, but perhaps there is an adaptive benefit to ultradian rhythms not meeting these expectations, which sets them functionally apart from circadian rhythms.
View Article and Find Full Text PDFThe MuCAYA Study-Influence of Physical Activity and Metabolic Parameters on the Structure and Function of the Cardiovascular System in Young Athletes.
CJC Open
December 2024
Department of Health and Sport Sciences, Institute of Preventive Pediatrics, Technical University of Munich (TUM) School of Medicine and Health, TUM, Munich, Germany.
Exercise has a significant impact on the cardiovascular (CV) health of children and adolescents, with resultant alterations in CV structure and function being evident, even at an early age. Engagement in regular, moderate physical activity (PA) is associated with long-term CV health benefits and a reduced risk of CV disease and mortality later in life. However, competitive sports often involve PA training intensities that are beyond recommended levels for young athletes, potentially leading to adverse CV outcomes.
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