Sphingosine 1-phosphate (S1P) receptors (S1PRs) belong to the class A family of G protein-coupled receptors (GPCRs). S1PRs are widely expressed on many cell types, including those of the immune, cardiovascular, and central nervous systems. The S1PR family is rapidly gaining attention as an important mediator of many cellular processes, including cell differentiation, migration, survival, angiogenesis, calcium homeostasis, inflammation and immunity. Importantly, S1PRs are known drug targets for multiple sclerosis (MS), for which the newly developed oral therapy fingolimod, an S1PR modulator, has recently been approved for clinical use. Much progress has also recently been made in the field of structural biology and in the modeling of heterotrimeric GPCRs allowing the crystal structure of the S1PR1 subtype to be elucidated and key interactions defined. Here, we outline the structure and function of S1PR1, highlighting the key residues involved in receptor activation, signaling, transmembrane interactions, ligand binding, post-translational modification, and protein-protein interactions.
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http://dx.doi.org/10.1016/j.tips.2013.05.002 | DOI Listing |
J Clin Invest
January 2025
Division of Pediatric Hematology/Oncology, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, United States of America.
Although nucleoporin 98 (NUP98) fusion oncogenes often drive aggressive pediatric leukemia by altering chromatin structure and expression of HOX genes, underlying mechanisms remain elusive. Here, we report that a Hoxb-associated lncRNA HoxBlinc was aberrantly activated in NUP98-PHF23 fusion-driven leukemias. HoxBlinc chromatin occupancies led to elevated MLL1 recruitment and aberrant homeotic topologically associated domains (TADs) that enhanced chromatin accessibilities and activated homeotic/hematopoietic oncogenes.
View Article and Find Full Text PDFElife
January 2025
Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, United States.
Sensory experience during developmental critical periods has lifelong consequences for circuit function and behavior, but the molecular and cellular mechanisms through which experience causes these changes are not well understood. The antennal lobe houses synapses between olfactory sensory neurons (OSNs) and downstream projection neurons (PNs) in stereotyped glomeruli. Many glomeruli exhibit structural plasticity in response to early-life odor exposure, indicating a general sensitivity of the fly olfactory circuitry to early sensory experience.
View Article and Find Full Text PDFACS Nano
January 2025
International Center for Quantum Design of Functional Materials (ICQD), Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei 230026, China.
Synergy between superconductivity and ferromagnetism may offer great opportunities in nondissipative spintronics and topological quantum computing. Yet at the microscopic level, the exchange splitting of the electronic states responsible for ferromagnetism is inherently incompatible with the spin-singlet nature of conventional superconducting Cooper pairs. Here, we exploit the recently discovered van der Waals ferromagnets as enabling platforms with marvelous controllability to unravel the myth between ferromagnetism and superconductivity.
View Article and Find Full Text PDFPharmacol Rep
January 2025
Razi Drug Research Centre, Iran University of Medical Sciences (IUMS), Tehran, Iran.
Melatonin, renowned for regulating sleep-wake cycles, also exhibits notable anti-aging properties for the skin. Synthesized in the pineal gland and various tissues including the skin, melatonin's efficacy arises from its capacity to combat oxidative stress and shield the skin from ultraviolet (UV)-induced damage. Moreover, it curbs melanin production, thereby potentially ameliorating hyperpigmentation.
View Article and Find Full Text PDFMol Divers
January 2025
Integrated Drug Discovery Centre, Department of Pharmaceutical Chemistry, Acharya & BM Reddy College of Pharmacy, Bengaluru, 560107, Karnataka, India.
Discoidin domain receptors (DDR) are categorized under tyrosine kinase receptors (RTKs) and play a crucial role in various etiological conditions such as cancer, fibrosis, atherosclerosis, osteoarthritis, and inflammatory diseases. The structural domain rearrangement of DDR1 and DDR2 involved six domains of interest namely N-terminal DS, DS-like, intracellular juxtamembrane, transmembrane juxtamembrane, extracellular juxtamembrane intracellular kinase domain, and the tail portion contains small C-tail linkage. DDR has not been explored to a wide extent to be declared as a prime target for any particular pathological condition.
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