Lamp1 is a type I transmembrane glycoprotein that is localized primarily in lysosomes and late endosomes. Newly synthesized molecules are mostly transported from the trans-Golgi network directly to endosomes and then to lysosomes. A minor pathway involves transport via the plasma membrane. The 11-amino acid cytoplasmic tail of lamp1 contains a tyrosine-based motif that has been previously shown to mediate sorting in the trans-Golgi network and rapid internalization at the plasma membrane. We studied whether this motif also mediates sorting in endosomes. We found that mutant forms of lamp1 in which all the amino acids of the cytoplasmic tail were modified except for the RKR membrane anchor and the YXXI sorting motif still localized to dense lysosomes, indicating that the YXXI motif is sufficient to confer proper intracellular targeting. However, when the spacing of the YXXI motif relative to the membrane was changed by deleting one amino acid or adding five amino acids, lysosomal targeting was almost completely abolished. Kinetic studies showed that these mutants were trapped in a recycling pathway, involving trafficking between the plasma membrane and early endocytic compartments. These findings indicate that the YXXI signal of lamp1 is recognized at several sorting sites, including the trans-Golgi network, the plasma membrane, and the early/sorting endosomes. Small changes in the spacing of this motif relative to the membrane dramatically impair sorting in the early/sorting endosomes but have only a modest effect on internalization at the plasma membrane. The spacing of sorting signals relative to the membrane may prove to be an important determinant in the functioning of these signals.
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http://dx.doi.org/10.1083/jcb.132.4.565 | DOI Listing |
BMC Vet Res
January 2025
Department of Animal Production, Faculty of Agriculture, Mansoura University, Mansoura, 35516, Egypt.
Phytochemicals have been effectively used to enhance the growth and productivity of farm animals, while the potential roles of essential oils and their nano-emulsions are limited. This plan was proposed to investigate the impacts of orally administered moringa oil (MO) or its nano-emulsion (NMO) on the growth, physiological response, blood health, semen attributes, and sperm antioxidant-related genes in rams. A total of 15 growing Rahmani rams were enrolled in this study and allotted into three groups.
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January 2025
Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, China.
As one of the most commonly used general anesthetics (GAs) in surgery, numerous studies have demonstrated the detrimental effects of sevoflurane exposure on myelination in the developing and elderly brain. However, the impact of sevoflurane exposure on intact myelin structure in the adult brain is barely discovered. Here, we show that repeated sevoflurane exposure, but not single exposure, causes hypomyelination and abnormal ultrastructure of myelin sheath in the prefrontal cortex (PFC) of adult male mice, which is considered as a critical brain region for general anesthesia mediated consciousness change.
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January 2025
Obsidian Therapeutics, Cambridge, MA, USA.
Adoptive cell therapies (ACT) have shown reduced efficacy against solid tumor malignancies compared to hematologic malignancies, partly due to the immunosuppressive nature of the tumor microenvironment (TME). ACT efficacy may be enhanced with pleiotropic cytokines that remodel the TME; however, their expression needs to be tightly controlled to avoid systemic toxicities. Here we show T cells can be armored with membrane-bound cytokines with surface expression regulated using drug-responsive domains (DRDs) developed from the 260-amino acid protein human carbonic anhydrase 2 (CA2).
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January 2025
Neuroscience Graduate Program, The Ohio State University, Columbus, OH, 43210, USA.
Postpartum depression (PPD) affects up to 20% of new mothers and has adverse consequences for the well-being of both mother and child. Exposure to stress during pregnancy as well as dysregulation in the mesolimbic dopamine (DA) reward system and its upstream modulator oxytocin (OT) have been independently linked to PPD. However, no studies have directly examined DA or OT signaling in the postpartum brain after gestational stress.
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January 2025
Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt.
Yttrium oxide nanoparticles (YONPs) have emerged as a promising avenue for cancer therapy, primarily due to their distinctive properties that facilitate selective targeting of cancer cells. Despite their potential, the therapeutic effects of YONPs on human epidermoid skin cancer remain largely unexplored. This study was thus conducted to investigate the impact of YONPs on both human skin normal and cancer cells, with an emphasis on assessing their cytotoxicity, genotoxicity, and the mechanisms underlying these effects.
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