Showing papers by "Laura Soldati published in 2017"
TL;DR: In conclusion, meal timing appears as a new potential target in weight control strategies, and therapeutic strategies should consider this contributor in the prevention of obesity.
39 citations
TL;DR: FLNA is downregulated in parathyroid tumors and parallels the CASR expression levels, which is involved in receptor expression, membrane localization and ERK signaling activation of both 990R and 990G CASR variants.
Abstract: Parathyroid tumors display reduced sensitivity to extracellular calcium ([Ca2+]o). [Ca2+]o activates calcium-sensing receptor (CASR), which interacts with the scaffold protein filamin A (FLNA). The study aimed to investigate: (1) the FLNA expression in human parathyroid tumors, (2) its effects on the CASR mRNA and protein expression, and (3) on ERK signaling activation, (4) the effect of the carboxy-terminal CASR variants and (5) of the treatment with the CASR agonist R568 on FLNA-mediated ERK phosphorylation in HEK293 cells. Full-length FLNA immunostaining was variably reduced in parathyroid tumors. Immunofluorescence showed that FLNA localized in membrane and cytoplasm and co-localized with CASR in parathyroid adenomas (PAds)-derived cells. Cleaved C-terminus FLNA fragment could also be detected in PAds nuclear protein fractions. In HEK293 cells transfected with 990R-CASR or 990G-CASR variants, silencing of endogenous FLNA reduced CASR mRNA levels and total and membrane-associated CASR proteins. In agreement, FLNA mRNA levels positively correlated with CASR expression in a series of 74 PAds; however, any significant correlation with primary hyperparathyroidism severity could be detected and FLNA transcript levels did not differ between PAds harboring 990R or 990G CASR variants. R568 treatment was efficient in restoring 990R-CASR and 990G-CASR sensitivity to [Ca2+]o in the absence of FLNA. In conclusion, FLNA is downregulated in parathyroid tumors and parallels the CASR expression levels. Loss of FLNA reduces CASR mRNA and protein expression levels and the CASR-induced ERK phosphorylation. FLNA is involved in receptor expression, membrane localization and ERK signaling activation of both 990R and 990G CASR variants.
14 citations
01 Jan 2017
TL;DR: Polymorphisms decreasing CaSR expression in renal tubular cells may increase risk for developing calcium oxalate kidney stones, and CaSR gene polymorphisms may modify the phenotype of healthy subjects and patients with primary and secondary hyperparathyroidism.
Abstract: The calcium-sensing receptor (CaSR) is a plasma membrane protein that senses calcium in the extracellular fluid. Cloned from bovine parathyroid cells in 1993, CaSR is mainly expressed in the parathyroid glands and renal distal tubules, and it enables these tissues to regulate parathyroid hormone secretion and calcium excretion, respectively, in response to changes in serum calcium. CaSR is also crucial for normal growth plate development and bone remodeling. Therefore CaSR is a key regulator of calcium homeostasis. Moreover, CaSR polymorphisms have been associated with serum calcium concentration and urine calcium excretion in humans. Polymorphisms decreasing CaSR expression in renal tubular cells may increase risk for developing calcium oxalate kidney stones. CaSR gene polymorphisms may modify the phenotype of healthy subjects and patients with primary and secondary hyperparathyroidism, and it may allow identification of individuals prone to developing kidney stones.
2 citations
TL;DR: Functional studies indicated increased activity of mutant receptor compared to the wild-type, and PCR amplification of CASR coding sequence and direct sequencing of PCR products showed a novel heterozygous deletion of a cytosine and a premature stop codon resulting in a truncation of the CaSR's C-tail.
2 citations