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An Alternative Mode of GPCR Transactivation: Activation of GPCRs by Adhesion GPCRs.
Int J Mol Sci
January 2025
Department of Microbiology and Immunology, Graduate School of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
G protein-coupled receptors (GPCRs), critical for cellular communication and signaling, represent the largest cell surface protein family and play important roles in numerous pathophysiological processes. Consequently, GPCRs have become a primary focus in drug discovery efforts. Beyond their traditional G protein-dependent signaling pathways, GPCRs are also capable of activating alternative signaling mechanisms, including G protein-independent signaling, biased signaling, and signaling crosstalk.
View Article and Find Full Text PDFThe TLR7/9 adaptors TASL and TASL2 mediate IRF5-dependent antiviral responses and autoimmunity in mouse.
Nat Commun
January 2025
Department of Immunobiology, University of Lausanne, Epalinges, Switzerland.
Endosomal nucleic acid sensing by Toll-like receptors (TLRs) is central to antimicrobial immunity and several autoimmune conditions such as systemic lupus erythematosus (SLE). The innate immune adaptor TASL mediates, via the interaction with SLC15A4, the activation of IRF5 downstream of human TLR7, TLR8 and TLR9, but the pathophysiological functions of this axis remain unexplored. Here we show that SLC15A4 deficiency results in a selective block of TLR7/9-induced IRF5 activation, while loss of TASL leads to a strong but incomplete impairment, which depends on the cell type and TLR engaged.
View Article and Find Full Text PDFUnderstanding the Myelin Ratio from First Principles, Its Derivation, Uses and Artifacts.
ASN Neuro
January 2025
Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, USA.
In light of the increasing importance for measuring myelin ratios - the ratio of axon-to-fiber (axon + myelin) diameters in myelin internodes - to understand normal physiology, disease states, repair mechanisms and myelin plasticity, there is urgent need to minimize processing and statistical artifacts in current methodologies. Many contemporary studies fall prey to a variety of artifacts, reducing study outcome robustness and slowing development of novel therapeutics. Underlying causes stem from a lack of understanding of the myelin ratio, which has persisted more than a century.
View Article and Find Full Text PDFIRAP Drives Ribosomal Degradation to Refuel Energy for Platelet Activation during Septic Thrombosis.
Adv Sci (Weinh)
January 2025
State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, China.
Platelets play crucial roles in multiple pathophysiological processes after energy-dependent activation. It is puzzling how such a small cellular debris has abundant energy supply. In this study, it is shown that insulin-regulated aminopeptidase (IRAP), a type II transmembrane protein, is a key regulator for platelet activation by promoting energy regeneration during septic thrombosis.
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