Polypeptide N-Acetylgalactosaminyl transferase 14 (GALNT14) plays important roles in cancer progression and chemotherapy response. Here, we show that GALNT14 is highly expressed in pancreatic β cells and regulates β cell function and growth. We found that the expression level of Ganlt14 was significantly decreased in the primary islets from three rodent type-2 diabetic models. Single-Cell sequencing defined that Galnt14 was mainly expressed in β cells of mouse islets. Galnt14 knockout (G14KO) INS-1 cell line, constructed by using CRISPR/Cas9 technology were growth normal, but showed blunt shape, and increased basal insulin secretion. Combined proteomics and glycoproteomics demonstrated that G14KO altered cell-to-cell junctions, communication, and adhesion. Insulin receptor (IR) and IGF1-1R were indirectly confirmed for GALNT14 substrates, contributed to diminished IGF1-induced p-AKT levels and cell growth in G14KO cells. Overall, this study uncovers that GALNT14 is a novel modulator in regulating β cells biology, providing a missing link of β cells O-glycosylation to diabetes development.
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http://dx.doi.org/10.1016/j.mce.2024.112269 | DOI Listing |
BMJ Case Rep
October 2024
Endocrinology, Rutgers New Jersey Medical School, Newark, New Jersey, USA.
Mol Cell Endocrinol
September 2024
Key Laboratory of Human Functional Genomics of Jiangsu Province, Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China. Electronic address:
Mol Cell Endocrinol
September 2024
Key Laboratory of Human Functional Genomics of Jiangsu Province, Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China. Electronic address:
Polypeptide N-Acetylgalactosaminyl transferase 14 (GALNT14) plays important roles in cancer progression and chemotherapy response. Here, we show that GALNT14 is highly expressed in pancreatic β cells and regulates β cell function and growth. We found that the expression level of Ganlt14 was significantly decreased in the primary islets from three rodent type-2 diabetic models.
View Article and Find Full Text PDFSci Adv
March 2024
Structural Biochemistry Unit, NIDCR, NIH, Bethesda, MD 20892, USA.
N-acetylgalactosaminyl-transferases (GalNAc-Ts) initiate mucin-type O-glycosylation, an abundant and complex posttranslational modification that regulates host-microbe interactions, tissue development, and metabolism. GalNAc-Ts contain a lectin domain consisting of three homologous repeats (α, β, and γ), where α and β can potentially interact with O-GalNAc on substrates to enhance activity toward a nearby acceptor Thr/Ser. The ubiquitous isoenzyme GalNAc-T1 modulates heart development, immunity, and SARS-CoV-2 infectivity, but its substrates are largely unknown.
View Article and Find Full Text PDFOncol Lett
December 2023
Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Fibrosarcoma is a highly malignant type of soft tissue sarcoma that currently lacks effective treatment options. Polypeptide N-acetylgalactosaminyltransferase 12 (GALNT12) belongs to the uridine diphosphate N-acetylgalactosamine gene family, which is involved in numerous biological processes of diseases, such as tumor progression. Its upregulated expression is closely associated with the development of colorectal cancer.
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