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G Protein-Coupled Receptor Heteromers in Brain: Functional and Therapeutic Importance in Neuropsychiatric Disorders.
Annu Rev Pharmacol Toxicol
January 2025
Department of Pharmacology and Toxicology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; email:
G protein-coupled receptors (GPCRs) represent the largest family of plasma membrane proteins targeted for therapeutic development. For decades, GPCRs were investigated as monomeric entities during analysis of their pharmacology or signaling and during drug development. However, a considerable body of evidence now indicates that GPCRs function as dimers or higher-order oligomers.
View Article and Find Full Text PDFThe multifaceted role of XCL1 in health and disease.
Protein Sci
February 2025
Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
The chemokine XC motif chemokine ligand 1 (XCL1) is an unusually specialized member of a conserved family of around 50 small, secreted proteins that are best known for their ability to stimulate the directional migration of cells. All chemokines adopt a very similar folded structure that binds a specific G protein-coupled receptor (GPCR), and most chemokines bind extracellular matrix glycosaminoglycans, often in a dimeric or oligomeric form. Owing in part to the lack of a disulfide bond that is conserved in all other chemokines, XCL1 interconverts between two distinct structures with distinct functions.
View Article and Find Full Text PDFOptogenetic control of mitochondrial aggregation and function.
Front Bioeng Biotechnol
January 2025
Department of Endocrinology, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Children's Health, Hangzhou, China.
The balance of mitochondrial fission and fusion plays an important role in maintaining the stability of cellular homeostasis. Abnormal mitochondrial fission and fragmentation have been shown to be associated with oxidative stress, which causes a variety of human diseases from neurodegeneration disease to cancer. Therefore, the induction of mitochondrial aggregation and fusion may provide an alternative approach to alleviate these conditions.
View Article and Find Full Text PDFThe EphA2 transmembrane receptor is a key regulator of cellular growth, differentiation, and motility, and its overexpression in various cancers positions it as a promising biomarker for clinical cancer management. EphA2 signaling is mediated through ligand-induced dimerization, which stabilizes its dimeric state via conformational changes in the extracellular region and is linked to the intracellular kinase region via the transmembrane (TM) domain. Similar to many receptor tyrosine kinases, the juxtamembrane (JM) region, located between the TM and catalytic domains, coordinates with the TM domain to facilitate signal transduction.
View Article and Find Full Text PDFQuantifying Monomer-Dimer Distribution of Nanoparticles from Uncorrelated Optical Images Using Deep Learning.
ACS Omega
January 2025
Nanotechnology, IoT and Applied Machine Learning Research Group, BRAC University, Kha 224 Bir Uttam Rafiqul Islam Avenue, Merul Badda, Dhaka 1212, Bangladesh.
Nanoparticles embedded in polymer matrices play a critical role in enhancing the properties and functionalities of composite materials. Detecting and quantifying nanoparticles from optical images (fixed samples-in vitro imaging) is crucial for understanding their distribution, aggregation, and interactions, which can lead to advancements in nanotechnology, materials science, and biomedical research. In this article, we propose an ensembled deep learning approach for automatic nanoparticle detection and oligomerization quantification in a polymer matrix for optical images.
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