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N-terminal fragment shedding contributes to signaling of the full-length adhesion receptor ADGRL3.
J Biol Chem
January 2025
Department of Psychiatry, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA; Department of Molecular Pharmacology and Therapeutics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, USA. Electronic address:
Most adhesion GPCRs undergo autoproteolytic cleavage during receptor biosynthesis, resulting in non-covalently bound N- and C-terminal fragments (NTF and CTF) that remain associated during receptor trafficking to the plasma membrane. While substantial evidence supports increased G protein signaling when just the CTF is expressed, there is an ongoing debate about whether NTF removal is required to initiate signaling in the context of the wild-type receptor. Here, we use adhesion GPCR latrophilin-3 (ADGRL3) as a model receptor to investigate tethered agonist-mediated activation.
View Article and Find Full Text PDFGasdermin D regulates the activation of EGFR in colorectal cancer.
J Transl Med
December 2024
Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China.
Background: Gasdermin D (GSDMD) is a key effector molecule that activates pyroptosis through its N terminal domain (GSDMD-NT). However, the roles of GSDMD in colorectal cancer (CRC) have not been fully explored. The role of the full-length GSDMD (GSDMD-FL) is also not clear.
View Article and Find Full Text PDFA soluble TLR5 is involved in the flagellin-MyD88-mediated immune response via regulation rather than activation in large yellow croaker (Larimichthys crocea).
Comp Biochem Physiol B Biochem Mol Biol
December 2024
State Key Laboratory of Mariculture Breeding, Fisheries College, Jimei University, Xiamen 361021, China. Electronic address:
Toll-like receptor 5 (TLR5) plays a crucial role in the immune response through recognizing bacterial flagellin. Some teleosts possess two forms of TLR5, including a canonical membrane TLR5 (TLR5M) ortholog and a piscine soluble TLR5 (TLR5S). In this report, the full-length cDNA sequences of Larimichthys crocea TLR5M (LcTLR5M) and TLR5S (LcTLR5S) were identified.
View Article and Find Full Text PDFCharacterization and functional analysis of interleukin-6 and its receptor subunits (IL-6Rα and IL-6Rβ) in the yellow drum, Nibea alibiflora.
Dev Comp Immunol
January 2025
National and Provincial Joint Laboratory of Exploration and Utilization of Marine Aquatic Genetic Resources, National Engineering Research Center of Marine Facilities Aquaculture, Zhejiang Ocean University, Zhoushan, 316022, PR China. Electronic address:
Interleukin 6 (IL-6) is one of the cytokines found to be multifunctional and biologically effective, regulating immune and inflammatory response by interacting with receptors to transmit signals. In this study, the full-length cDNAs of IL-6 (named as NaIL-6) and its receptors IL-6R and gp130 (named as NaIL-6Rα and NaIL-6Rβ) of Nibea albiflora were acquired and they possessed the typical symbolic motifs similar to its teleost orthologues in multiple sequence comparisons. The phylogenetic trees showed that NaIL-6 and its receptors clustered with their counterparts in bony fish, and had the closest affinity to Larimichthys crocea.
View Article and Find Full Text PDFThe vectors went in two-by-two: Transduction efficiency and tolerability of dual and triple rAAV vector delivery following intravitreal injection for genome-editing applications.
Exp Eye Res
December 2024
Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, WI, 53226, USA; Department of Ophthalmology & Visual Sciences, Medical College of Wisconsin, WI, 53226, USA. Electronic address:
Genome or prime editing has become a promising tool for the treatment of hereditary disorders affecting the inner retina, such as dominant optic neuropathies. In vivo delivery of gene editors, such as Cas9, is typically achieved using recombinant adeno-associated virus (rAAV) vectors, which have a broad range of cellular tropisms and are well tolerated following intravitreal administration. Owing to the large size of gene editing constructs and the limited carrying capacity of rAAV (<5.
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