G alpha(q)-mediated plasma membrane translocation of sphingosine kinase-1 and cross-activation of S1P receptors

Sphingosine-1-phosphate (S1P), formed by sphingosine kinases (SphKs), regulates cellular proliferation and migration by acting as an agonist at specific receptors or intracellularly. Since S1P's effects are probably dependent on subcellular localization of its formation and degradation, we have studied the influence of G protein-coupled receptors on the localization of SphK1. Activation of Gq-coupled receptors induced a profound, rapid (half-life 3-5 s) and long-lasting (> 2 h) translocation of SphK1 to the plasma membrane. This was mimicked by expression of constitutively active G protein alpha-subunits specifically of the Gq family. Classical Gq signalling pathways, or phosphorylation at Ser225, phospholipase D and Ca2+/calmodulin were not involved in M3 receptor-induced SphK1 translocation in HEK-293 cells. Translocation was associated with S1P receptor internalization, which was dependent on catalytic activity of SphK1 and S1P receptor binding and thus resulted from S1P receptor cross-activation. It is concluded that SphK1 is an important effector of Gq-coupled receptors, linking them via cross-activation of S1P receptors to G(i) and G12/13 signalling pathways.Michael ter Braak, Kerstin Danneberg, Karin Lichte, Kerstin Liphardt, Nicholas T. Ktistakis, Stuart M. Pitson, Timothy Hla, Karl H. Jakobs and Dagmar Meyer zu Heringdor

停留精巣の研究 第3報: 停留精巣患者における精巣内複合糖質の組織化学的研究

3～37歳の停留精巣患者23例の停留精巣および対側陰嚢内精巣において, 光顕組織化学的方法にて複合糖質の変化を観察し, さらに正常精巣組織と比較した.停留精巣精細管壁及び間質では, 正常精巣に比べ酸性ムコ多糖(精細管壁:コンドロイチン硫酸A及びC, 間質:コンドロイチン硫酸B)が減少し, 特に精細管壁において顕著であった.なお, 患側精細管上皮においては, 思春期前から思春期以後を通じ, グリコーゲン及びガラクトース含有量の減少が認められたThe complex carbohydrates in the undescended and contralateral scrotal testes of patients with cryptorchidism, were examined by light microscopic histochemical methods, in comparison with those of normal testes. In the undescended testes, histochemical reactions for acidic and neutral complex carbohydrates were apparently weaker than in the normal testes, especially pronounced in the seminiferous tubular walls. In the germinal and supporting cells of the undescended testes, the amount of galactose residues in the complex carbohydrates decreased from the prepubertal to post-pubertal periods. Periodic acid-Schiff reaction also revealed a decrease in the glycogen content in the germinal and supporting cells of the undescended testes from pre-pubertal to post-pubertal periods