Ca2+ entry via TRPC1 is essential for cellular differentiation and modulates secretion via the SNARE complex
| Autor: | Thad A. Rosenberger, Yuyang Sun, Lutz Brinbaumer, Pramod Sukumaran, Brij B. Singh, Kate J. Claycombe-Larson, Danielle Krout, Anne Schaar, James N. Roemmich |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
TRPC1 Cellular differentiation Leptin education Adipose tissue Adipokine Cell Biology Biology TEJIDO ADIPOSO Cell biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine chemistry OBESIDAD Adipocyte Secretion Adiponectin secretion 030217 neurology & neurosurgery SINDROME METABOLICO 030304 developmental biology |
| Zdroj: | Journal of Cell Science. 2019, 132 Repositorio Institucional (UCA) Pontificia Universidad Católica Argentina instacron:UCA |
| Popis: | Fil: Schaar, Anne. University of North Dakota. School of Medicine and Health Sciences. Department of Biomedical Science; Estados Unidos Fil: Sun, Yuyang. University of North Dakota. School of Medicine and Health Sciences. Department of Biomedical Science; Estados Unidos Fil: Sukumaran, Pramod. University of North Dakota. School of Medicine and Health Sciences. Department of Biomedical Science; Estados Unidos Fil: Rosenberger, Thad A. University of North Dakota. School of Medicine and Health Sciences. Department of Biomedical Science; Estados Unidos Fil: Krout, Danielle. Grand Forks Human Nutrition Research Center. United States Department of Agriculture. Agricultural Research Service; Estados Unidos Fil: Roemmich, James N. Grand Forks Human Nutrition Research Center. United States Department of Agriculture. Agricultural Research Service; Estados Unidos Fil: Brinbaumer, Lutz. National Institute of Environmental Health Sciences. Neurobiology Laboratory; Estados Unidos Fil: Brinbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina Fil: Claycombe-Larson, Kate. Grand Forks Human Nutrition Research Center. United States Department of Agriculture. Agricultural Research Service; Estados Unidos Fil: Singh, Brij B. University of North Dakota. School of Medicine and Health Sciences. Department of Biomedical Science; Estados Unidos Abstract: Properties of adipocytes, including differentiation and adipokine secretion, are crucial factors in obesity-associated metabolic syndrome. Here, we provide evidence that Ca2+ influx in primary adipocytes, especially upon Ca2+ store depletion, plays an important role in adipocyte differentiation, functionality and subsequently metabolic regulation. The endogenous Ca2+ entry channel in both subcutaneous and visceral adipocytes was found to be dependent on TRPC1-STIM1, and blocking Ca2+ entry with SKF96365 or using TRPC1-/- knockdown adipocytes inhibited adipocyte differentiation. Additionally, TRPC1-/- mice have decreased organ weight, but increased adipose deposition and reduced serum adiponectin and leptin concentrations, without affecting total adipokine expression. Mechanistically, TRPC1-mediated Ca2+ entry regulated SNARE complex formation, and agonist-mediated secretion of adipokine-loaded vesicles was inhibited in TRPC1-/- adipose. These results suggest an unequivocal role of TRPC1 in adipocyte differentiation and adiponectin secretion, and that loss of TRPC1 disturbs metabolic homeostasis.This article has an associated First Person interview with the first author of the paper. |
| Databáze: | OpenAIRE |
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