Exogenous L-fucose attenuates depression induced by chronic unpredictable stress: Implicating core fucosylation has an antidepressant potential.

Core fucosylation is one of the most essential modifications of the N-glycans, catalyzed by α1,6-fucosyltransferase (Fut8), which transfers fucose from guanosine 5'-diphosphate (GDP)-fucose to the innermost N-acetylglucosamine residue of N-glycans in an α1-6 linkage. Our previous studies demonstrated that lipopolysaccharide (LPS) can induce a more robust neuroinflammatory response in Fut8 homozygous knockout (KO) (Fut8) and heterozygous KO (Fut8) mice contrasted to the wild-type (Fut8) mice. Exogenous administration of L-fucose suppressed LPS-induced neuroinflammation.

-GlcNAcylation of Focal Adhesion Kinase Regulates Cell Adhesion, Migration, and Proliferation via the FAK/AKT Pathway.

Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase pivotal in cellular signal transduction, regulating cell adhesion, migration, growth, and survival. However, the regulatory mechanisms of FAK during tumorigenesis and progression still need to be fully understood. Our previous study demonstrated that -GlcNAcylation regulates integrin-mediated cell adhesion.

The acetylglucosaminyltransferase GnT-Ⅲ regulates erythroid differentiation through ERK/MAPK signaling.

Differentiation therapy is an alternative strategy used in treating chronic myelogenous leukemia to induce the differentiation of immature or cancerous cells toward mature cells and inhibit tumor cell proliferation. We aimed to explore N-glycans' roles in erythroid differentiation using the sodium butyrate (NaBu)-induced model of K562 cells (WT/NaBu cells). Here, using lectin blot, flow cytometry, real-time PCR, and mass spectrometry analyses, we demonstrated that the mRNA levels of N-acetylglucosaminyltransferase Ⅲ ((encoded by the MGAT3 gene) and its product (bisected N-glycans) were significantly increased during erythroid differentiation.

Quantitative orbital tightening for pain assessment using machine learning with DeepLabCut.

Pain assessment in animal models is essential for understanding mechanisms underlying pathological pain and developing effective pain medicine. The grimace scale (GS), facial expression features in pain such as orbital tightening (OT), is a valuable measure for assessing pain in animal models. However, the classical grimace scale for pain assessment is labor-intensive, subject to subjectivity and inconsistency, and is not a quantitative measure.

Core fucosylation within the Fc-FcγR degradation pathway promotes enhanced IgG levels via exogenous L-fucose.

α1,6-Fucosyltransferase (Fut8) is the enzyme responsible for catalyzing core fucosylation. Exogenous L-fucose upregulates fucosylation levels through the GDP-fucose salvage pathway. This study investigated the relationship between core fucosylation and immunoglobulin G (IgG) amounts in serum utilizing WT (Fut8), Fut8 heterozygous knockout (Fut8), and Fut8 knockout (Fut8) mice.

Specific sialylation of N-glycans and its novel regulatory mechanism.

Altered glycosylation is a common feature of cancer cells. Some subsets of glycans are found to be frequently enriched on the tumor cell surface and implicated in different tumor phenotypes. Among these, changes in sialylation have long been associated with metastatic cell behaviors such as invasion and enhanced cell survival.

The K346T mutant of GnT-III bearing weak in vitro and potent intracellular activity.

Background: N-Acetylglucosaminyltransferase-III (GnT-III, also designated MGAT3) catalyzes the formation of a specific N-glycan branch, bisecting GlcNAc, in the Golgi apparatus. Bisecting GlcNAc is a key residue that suppresses N-glycan maturation and is associated with the pathogenesis of cancer and Alzheimer's disease. However, it remains unclear how GnT-III recognizes its substrates and how GnT-III activity is regulated in cells.

Importance of PTM of FLT3 in acute myeloid leukemia.

FMS-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase expressed in hematopoietic cells. Internal-tandem duplication domain (ITD) mutation and tyrosine kinase domain (TKD) mutation are the two most common mutations in acute myeloid leukemia (AML). Post-translational modifications (PTMs) of FLT3, such as glycosylation and ubiquitination, have been shown to impact various aspects of the protein in both wild-type (WT) and mutant forms of FLT3.

Assessment of orofacial nociceptive behaviors of mice with the sheltering tube method: Oxaliplatin-induced mechanical and cold allodynia in orofacial regions.

Preclinical studies on pathological pain rely on the von Frey test to examine changes in mechanical thresholds and the acetone spray test to determine alterations in cold sensitivity in rodents. These tests are typically conducted on rodent hindpaws, where animals with pathological pain show reliable nocifensive responses to von Frey filaments and acetone drops applied to the hindpaws. Pathological pain in orofacial regions is also an important clinical problem and has been investigated with rodents.

Novel regulatory mechanisms of N-glycan sialylation: Implication of integrin and focal adhesion kinase in the regulation.

Background: Sialylation of glycoproteins, including integrins, is crucial in various cancers and diseases such as immune disorders. These modifications significantly impact cellular functions and are associated with cancer progression. Sialylation, catalyzed by specific sialyltransferases (STs), has traditionally been considered to be regulated at the mRNA level.

An emerging role of N-glycosylation in cancer chemoresistance.

Chemoresistance poses a significant obstacle in the effective treatment of cancer, limiting the success of chemotherapy regimens. N-glycosylation, the most important post-translational modification (PTM), plays multifaceted roles in the intricate landscape of cancer progression, particularly drug resistance in cancer cells. This review explores the complex relationship between N-glycosylation and chemoresistance in cancer.

Fucosylation inhibitor 6-alkynylfucose enhances the ATRA-induced differentiation effect on acute promyelocytic leukemia cells.

For acute promyelocytic leukemia (APL), differentiation therapy with all-trans retinoic acid (ATRA) is well established. However, the narrow application and tolerance development of ATRA remain to be improved. In this study, we investigated the effects of combinations of glycosylation inhibitors with ATRA to achieve better efficiency than ATRA alone.

Distinct local and global functions of mouse Aβ low-threshold mechanoreceptors in mechanical nociception.

The roles of Aβ low-threshold mechanoreceptors (LTMRs) in transmitting mechanical hyperalgesia and in alleviating chronic pain have been of great interest but remain contentious. Here we utilized intersectional genetic tools, optogenetics, and high-speed imaging to specifically examine functions of Split labeled mouse Aβ-LTMRs in this regard. Genetic ablation of Split-Aβ-LTMRs increased mechanical nociception but not thermosensation in both acute and chronic inflammatory pain conditions, indicating a modality-specific role in gating mechanical nociception.

Effects of inflammation on the properties of Nav1.8-ChR2-positive and Nav1.8-ChR2-negative afferent mechanoreceptors in the hindpaw glabrous skin of mice.

We recently used Nav1.8-ChR2 mice in which Nav1.8-expressing afferents were optogenetically tagged to classify mechanosensitive afferents into Nav1.

ASICs mediate fast excitatory synaptic transmission for tactile discrimination.

Tactile discrimination, the ability to differentiate objects' physical properties such as texture, shape, and edges, is essential for environmental exploration, social interaction, and early childhood development. This ability heavily relies on Merkel cell-neurite complexes (MNCs), the tactile end-organs enriched in the fingertips of humans and the whisker hair follicles of non-primate mammals. Although recent studies have advanced our knowledge on mechanical transduction in MNCs, it remains unknown how tactile signals are encoded at MNCs.

Core fucosylation regulates the ovarian response via FSH receptor during follicular development.

Introduction: Ovarian low response to follicle-stimulating hormone (FSH) causes infertility featuring hypergonadotropic hypogonadism, ovarian failure, and/or defective ovarian response.

Objectives: N-glycosylation is essential for FSH receptor (FSHR). Core fucosylation catalyzed by fucosyltransferase 8 (FUT8) is the most common N-glycosylation.

Integrin α6β4 Confers Doxorubicin Resistance in Cancer Cells by Suppressing Caspase-3-Mediated Apoptosis: Involvement of N-Glycans on β4 Integrin Subunit.

Drug resistance is a major obstacle to successful cancer treatment. Therefore, it is essential to understand the molecular mechanisms underlying drug resistance to develop successful therapeutic strategies. α6β4 integrin confers resistance to apoptosis and regulates the survival of cancer cells; however, it remains unclear whether α6β4 integrin is directly involved in chemoresistance.

Exogenous l-fucose attenuates neuroinflammation induced by lipopolysaccharide.

α1,6-Fucosyltransferase (Fut8) catalyzes the transfer of fucose to the innermost GlcNAc residue of N-glycan to form core fucosylation. Our previous studies showed that lipopolysaccharide (LPS) treatment highly induced neuroinflammation in Fut8 homozygous KO (Fut8) or heterozygous KO (Fut8) mice, compared with the WT (Fut8) mice. To understand the underlying mechanism, we utilized a sensitive inflammation-monitoring mouse system that contains the human interleukin-6 (hIL6) bacterial artificial chromosome transgene modified with luciferase (Luc) reporter cassette.

A highly specific antibody against the core fucose of the N-glycan in IgG identifies the pulmonary diseases and its regulation by CCL2.

Glycan structure is often modulated in disease or predisease states, suggesting that such changes might serve as biomarkers. Here, we generated a monoclonal antibody (mAb) against the core fucose of the N-glycan in human IgG. Notably, this mAb can be used in Western blotting and ELISA.

Effect of N-glycosylation on constitutive signal transduction by mutated cytokine receptor-like factor 2.

Background: Cytokine receptor-like factor 2 (CRLF2) is a subunit of the receptor for thymic stromal lymphopoietin (TSLP). A somatic mutation (insEIM) in the transmembrane domains of CRLF2 has been identified in acute lymphocytic leukemia (ALL), and Glu-Ile-Met (EIM) CRLF2 induces constitutive activation of signals. However, the signaling mechanism remains unclear.

Focal-adhesion kinase regulates the sialylation of N-glycans via the PI4KIIα-PI4P pathway.

Sialylation is a terminal glycosylated modification of glycoproteins that regulates critical biological events such as cell adhesion and immune response. Our previous study showed that integrin α3β1 plays a crucial role in regulating the sialylation of N-glycans. However, the underlying mechanism for the regulation remains unclear.