Ligand-dependent localization and intracellular stability of sigma-1 receptors in CHO-K1 cells.
Ligand-dependent localization and intracellular stability of sigma-1 receptors in CHO-K1 cells.
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DOI：
10.1186/1750-2187-2-8
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发表时间：
2007-09-20
影响因子：
--
通讯作者：
Ruoho AE
中科院分区：
文献类型：
--
作者：
Mavlyutov TA;Ruoho AE
Sigma-1受体可能通过调节离子通道的活性参与神经元活动的调节。Sigma-1受体也在癌细胞的生长和转移中发挥作用。细胞内sigma-1受体的分布与鞘脂富集结构域有关。我们报道，在CHO-K1细胞中，sigma-1受体靶向与Talin和Kv1.4钾通道共定位的局灶粘附接触（FAC）。应用sigma-1受体配体和丝状肌动蛋白（F-actin）与phalloidin聚合可显著提高FAC中sigma-1受体的水平。在有sigma-1受体的情况下，经phalloidin治疗，FAC的总长度（通过黏附标记物talin测量）同时增加。然而，只有sigma-1受体配体导致FAC中sigma-1受体的增加，而不依赖于talin。此外，一种新的方法被用来评估CHO-K1细胞中内源性sigma-1受体的半衰期，测量结果至少为72小时。配体激活的sigma-1受体从储存在内质网脂筏中的受体池转运到FAC，可能是为了抑制Kv1.4通道。在CHO-K1细胞中，肌动蛋白丝的稳定对于将sigma-1受体靶向黏附接触可能是重要的。
Sigma-1 receptors are involved in regulation of neuronal activities presumably through regulation of the activity of ion channels. Sigma-1 receptors also play a role in growth and metastasis of cancerous cells. Intracellular distribution of sigma-1 receptors have been linked to sphingolipid-enriched domains. We report that in CHO-K1 cells sigma-1 receptors target to focal adhesion contacts (FAC) where they colocalize with Talin and Kv1.4 potassium channels. The levels of sigma-1 receptors in the FAC were significantly increased by application of sigma-1 receptor ligands and by filamentous actin (F-actin) polymerization with phalloidin. The total length of FAC (measured by the focal adhesion marker, talin) was concomitantly increased in the presence of sigma-1 receptors upon phalloidin treatment. Only sigma-1 receptor ligands, however, resulted in an increase of sigma-1 receptors in the FAC, independent of talin. Additionally, a novel approach was utilized to allow an assessment of the half life of endogenous sigma-1 receptors in CHO-K1 cells, which was measured to be at least 72 hours. Ligand activated sigma-1 receptors translocate into FAC from a pool of receptors stored in ER lipid rafts presumably for inhibition of Kv1.4 channels. Stabilization of actin filaments is likely to be important for targeting sigma-1 receptors to Focal Adhesion Contacts in CHO-K1 cells.