MSAP enhances migration of C6 glioma cells through phosphorylation of the myosin regulatory light chain
MSAP enhances migration of C6 glioma cells through phosphorylation of the myosin regulatory light chain
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DOI：
10.1007/s00018-005-5055-x
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发表时间：
2005-06-01
影响因子：
8
通讯作者：
Lindholm, D
中科院分区：
文献类型：
--
作者：
Bornhauser, BC;Lindholm, D
细胞运动的一个关键调节机制是控制肌球蛋白活性，在非肌肉细胞中，肌球蛋白活性由肌球蛋白调节轻链（MRLC）的磷酸化决定。在这里，我们表明，MRLC相互作用蛋白（MIR）相互作用鞘脂激活蛋白样蛋白（MSAP）增强细胞在成纤维细胞和大鼠C6胶质瘤细胞的迁移，通过增加MRLC磷酸化。MSAP的过表达增强了胶质瘤细胞的运动性，在基质胶侵袭室和使用划痕试验。通过RNA干扰下调MSAP显著降低胶质瘤细胞的迁移和MRLC的磷酸化。ML-7对相应MRLC激酶的抑制并不影响MSAP过表达细胞的迁移。目前的结果表明，MSAP通过增强MRLC磷酸化来控制胶质瘤细胞迁移。这种作用不依赖于MRLC激酶的活性。因此，MSAP是一种新的细胞运动调节剂，影响神经胶质瘤细胞和可能的其他肿瘤的迁移。
A key regulatory mechanism in cell motility is the control of myosin activity, which in non-muscle cells is determined by phosphorylation of the myosin regulatory light chain (MRLC). Here we show that MRLC-interacting protein (MIR)-interacting saposin-like protein (MSAP) enhances cell spreading in fibroblasts and migration of rat C6 glioma cells through increases in MRLC phosphorylation. Overexpression of MSAP enhanced the motility of glioma cells measured in matrigel invasion chambers and using a scratch assay. Downregulation of MSAP by RNA interference significantly decreased glioma cell migration and phosphorylation of MRLC. Inhibition of the corresponding MRLC kinase by ML-7 did not affect migration of MSAP-overexpressing cells. The present results show that MSAP controls glioma cell migration via enhancement of MRLC phosphorylation. This effect is independent of the activity of MRLC kinase. Thus, MSAP is a novel modulator of cell motility that influences migration of glioma cells and possibly other tumors.