Involvement of the muscarinic acetylcholine receptor in inhibition of cell migration.
Involvement of the muscarinic acetylcholine receptor in inhibition of cell migration.
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毒蕈碱乙酰胆碱受体参与抑制细胞迁移。
DOI：
10.1016/s0006-2952(01)00901-7
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发表时间：
2002
影响因子：
5.8
通讯作者：
Williams,CarolL
中科院分区：
文献类型：
--
作者：
Varker,KimberlyA;Williams,CarolL
已知G蛋白偶联受体的激活刺激细胞迁移，但尚未鉴定抑制细胞迁移的受体介导的信号。我们研究了转染人M3胆碱能乙酰胆碱受体（mAChR）的中国仓鼠卵巢（CHO）细胞的迁移调节能力。单细胞迁移的胶体金应用到纤连蛋白包被的板，和视频显微镜用于测量细胞的扩散和迁移。激活M3 mAChR与激动剂卡巴胆碱被发现抑制细胞迁移，而直接激活蛋白激酶C（PKC）与PMA被发现刺激迁移。发现卡巴胆碱和PMA处理的细胞的细胞粘附和扩散的量是相等的。用Go 6976（C24 H18 N4 O）选择性灭活常规PKC亚型可消除PMA介导的细胞迁移增加。相比之下，mAChR介导的迁移减少没有改变Go 6976，但被取消时，新的和传统的PKC亚型被钙磷蛋白C或白屈菜红碱灭活。这些结果表明，参与传统的PKC亚型在迁移的刺激和新的PKC亚型在迁移的抑制。卡巴胆碱-但不是PMA-处理的细胞表现出细长的形态，让人联想到迁移细胞，不能脱离其后缘从底层。同样，卡巴胆碱处理的细胞脱离不容易从纤连蛋白比对照或PMA处理的细胞时，整合素的活性被削弱的螯合的Ca 2+和Mg 2+。最后，卡巴胆碱诱导的细胞脱落减少后，保留与Go 6976抑制常规PKC亚型，但被废除的治疗与calphostin C或白屈菜红碱。这些发现表明，mAChR活化降低了细胞从基质分离的能力，导致迁移减少。这与PMA直接激活PKC相反，PMA刺激迁移。
Activation of G protein-coupled receptors is known to stimulate cell migration, but receptor-mediated signals inhibiting cell migration have not been identified. We investigated the ability of transfected human M3muscarinic acetylcholine receptors (mAChR) to regulate the migration of Chinese hamster ovary (CHO) cells. Single cells migrated on colloidal gold applied to fibronectin-coated plates, and videomicroscopy was used to measure cell spreading and migration. Activation of M3mAChR with the agonist carbachol was found to inhibit cell migration, whereas direct activation of protein kinase C (PKC) with PMA was found to stimulate migration. The amount of cell adhesion and spreading was found to be equivalent for carbachol- and PMA-treated cells. Selective inactivation of conventional PKC isoforms with Go6976 (C24H18N4O) abolished the PMA-mediated increase in cell migration. In contrast, the mAChR-mediated decrease in migration was not altered by Go6976, but was abolished when both novel and conventional PKC isoforms were inactivated by calphostin C or chelerythrine. These findings suggest involvement of conventional PKC isoforms in the stimulation of migration and of novel PKC isoforms in the inhibition of migration. Carbachol- but not PMA-treated cells exhibited an elongated morphology reminiscent of migrating cells that cannot detach their trailing edges from the substratum. Similarly, carbachol-treated cells detached less readily from fibronectin than control or PMA-treated cells when integrin activity was diminished by the chelation of Ca2+and Mg2+. Finally, the carbachol-induced diminution of cell detachment was preserved after inhibition of the conventional PKC isoforms with Go6976, but was abrogated by treatment with either calphostin C or chelerythrine. These findings suggest that mAChR activation diminishes the ability of cells to detach from the substratum, resulting in diminished migration. This is in contrast to the direct activation of PKC with PMA, which stimulates migration.
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DOI：
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发表时间：
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期刊：
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影响因子：
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作者：
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发表时间：
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影响因子：
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作者：
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