Department of Basic Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, Obihiro Hokkaido, 080-8555, Japan.
J Cell Biochem. 2012 May;113(5):1654-62. doi: 10.1002/jcb.24034.
The sensing of the nutritional level of the body fluid is pivotal for maintaining homeostasis in animals. However, it is not yet understood how the cells detect nutritional levels. In the present study, we examined the function of umami taste receptor, which has a dimeric protein structure composed of Tas1r1 and Tas1r3, as amino acid sensor in the cells. We found that deprivation of amino acids induced neurite outgrowth in N1E-115 cells. The neurite outgrowth was inhibited by almost all of the amino acids tested. To investigate the involvement of the umami taste receptor, siRNA against each of Tas1r1 or Tas1r3 was administered, resulting in suppression of the inhibitory effects of amino acids on neurite outgrowth. In addition, inosine 5'-monophosphate, which potentiates the response to amino acids in the taste cells, enhanced the inhibitory effect of glutamine on neurite outgrowth. These results suggest that Tas1r1 + 3 functions as an amino acid sensor in N1E-115 cells. Because glutamine increased intracellular cAMP concentration, we investigated the involvement of the Gαs subunit of the heterotrimeric G protein in signal transduction. The treatments to inhibit the Gαs subunit significantly suppressed the increase of intracellular cAMP concentration induced by glutamine and the inhibitory effect of amino acids on neurite outgrowth. In addition, the reagents for increasing intracellular cAMP concentration inhibited neurite outgrowth induced by deprivation of amino acids. We concluded that Tas1r1 + 3 functions as an amino acid sensor and activates the intracellular signaling pathway through the Gαs subunit in N1E-115 cells.
体液营养水平的感知对于动物维持体内平衡至关重要。然而，细胞如何检测营养水平还不清楚。在本研究中，我们研究了鲜味味觉受体的功能，鲜味味觉受体由 Tas1r1 和 Tas1r3 组成二聚体蛋白结构，作为细胞中的氨基酸传感器。我们发现，氨基酸剥夺诱导 N1E-115 细胞的神经突生长。神经突生长被几乎所有测试的氨基酸抑制。为了研究鲜味味觉受体的参与，用 Tas1r1 或 Tas1r3 的 siRNA 处理，导致氨基酸对神经突生长的抑制作用被抑制。此外，肌苷 5'-单磷酸，增强味觉细胞对氨基酸的反应，增强谷氨酰胺对神经突生长的抑制作用。这些结果表明 Tas1r1 + 3 在 N1E-115 细胞中作为氨基酸传感器发挥作用。因为谷氨酰胺增加细胞内 cAMP 浓度，我们研究了异三聚体 G 蛋白的 Gαs 亚基在信号转导中的参与。抑制 Gαs 亚基的处理显著抑制了谷氨酰胺诱导的细胞内 cAMP 浓度增加和氨基酸对神经突生长的抑制作用。此外，增加细胞内 cAMP 浓度的试剂抑制了氨基酸剥夺诱导的神经突生长。我们得出结论，Tas1r1 + 3 在 N1E-115 细胞中作为氨基酸传感器发挥作用，并通过 Gαs 亚基激活细胞内信号通路。
