TY - JOUR
T1 - Ca2+ entry via TRPC1 is essential for cellular differentiation and modulates secretion via the SNARE complex
AU - Schaar, Anne
AU - Sun, Yuyang
AU - Sukumaran, Pramod
AU - Rosenberger, Thad A.
AU - Krout, Danielle
AU - Roemmich, James N.
AU - Brinbaumer, Lutz
AU - Claycombe-Larson, Kate
AU - Singh, Brij B.
N1 - Funding Information:
This work was funded by grant support from the National Institute of Dental and Craniofacial Research (R01DE017102; R01 DE022765) awarded to B.B.S., the ND EPSCoR through National Science Foundation (IIA-1355466) awarded to A.S., the U.S. Department of Agriculture Agricultural Research Service Project #3062-51000-052-00D awarded to K.C.-L. and Z01-636 ES-101684 to L.B. The funders (NIH/ USDA) had no further role in study design, data analysis, and/or interpretation of the data. Deposited in PMC for immediate release.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - 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.
AB - 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.
KW - Adipocyte differentiation
KW - Adiponectin secretion
KW - Ca entry
KW - Metabolic homeostasis
KW - TRPC1
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U2 - 10.1242/jcs.231878
DO - 10.1242/jcs.231878
M3 - Article
C2 - 31182642
AN - SCOPUS:85069265704
VL - 132
JO - Journal of Cell Science
JF - Journal of Cell Science
SN - 0021-9533
IS - 13
M1 - 231878
ER -