Sorice Maurizio, Molinari Sabrina, Di Marzio Luisa, Mattei Vincenzo, Tasciotti Vincenzo, Ciarlo Laura, Hiraiwa Masao, Garofalo Tina, Misasi Roberta
Dipartimento di Medicina Sperimentale, Sapienza University, Rome, Italy.
FEBS J. 2008 Oct;275(19):4903-12. doi: 10.1111/j.1742-4658.2008.06630.x.
Prosaposin is a neurotrophic factor that has been demonstrated to mediate trophic signalling events in different cell types; it distributes to surface membranes of neural cells and also exists as a secreted protein in different body fluids. Prosaposin was demonstrated to form tightly bound complexes with a variety of gangliosides, and a functional role has been suggested for ganglioside-prosaposin complexes. In this work, we provide evidence that exogenous prosaposin triggers a signal cascade after binding to its target molecules on lipid rafts of pheochromocytoma PC12 cell plasma membranes, as revealed by scanning confocal microscopy and linear sucrose gradient analysis. In these cells, prosaposin is able to induce extracellular signal-regulated kinase phosphorylation, sphingosine kinase activation, and consequent cell death prevention, acting through lipid rafts. These findings point to the role of lipid rafts in the prosaposin-triggered signalling pathway, thus supporting a role for this factor as a new component of the multimolecular signalling complex involved in the neurotrophic response.
前体唾液酸蛋白是一种神经营养因子，已被证明可介导不同细胞类型中的营养信号事件；它分布于神经细胞的表面膜，并且也作为一种分泌蛋白存在于不同的体液中。前体唾液酸蛋白被证明可与多种神经节苷脂形成紧密结合的复合物，并且有人提出神经节苷脂 - 前体唾液酸蛋白复合物具有功能作用。在这项研究中，我们提供的证据表明，如通过扫描共聚焦显微镜和线性蔗糖梯度分析所揭示的，外源性前体唾液酸蛋白在与嗜铬细胞瘤PC12细胞质膜脂筏上的靶分子结合后会触发信号级联反应。在这些细胞中，前体唾液酸蛋白能够诱导细胞外信号调节激酶磷酸化、鞘氨醇激酶激活，并因此通过脂筏作用防止细胞死亡。这些发现指出了脂筏在前体唾液酸蛋白触发的信号通路中的作用，从而支持了该因子作为参与神经营养反应的多分子信号复合物新组分的作用。
