Integrin and cytoskeletal involvement in signalling cell volume changes to glutamine transport in rat skeletal muscle
Integrin and cytoskeletal involvement in signalling cell volume changes to glutamine transport in rat skeletal muscle
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DOI：
10.1111/j.1469-7793.1998.481be.x
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发表时间：
1998-10-15
影响因子：
5.5
通讯作者：
Taylor, PM
中科院分区：
文献类型：
--
作者：
Low, SY;Taylor, PM
1. 肌肉谷氨酰胺转运通过依赖于活性磷脂酰肌醇 3-激酶的机制响应细胞体积的变化而受到调节。我们研究了这种机制需要细胞外基质（ECM）、整合素和细胞骨架之间相互作用作为机械化学转导系统的组成部分的可能性。2．使用骨骼肌细胞，我们研究了（a）通过使用整合素结合肽 GRGDTP 和失活肽 GRGESP 作为对照来失活整合素-基质相互作用，以及（b）使用秋水仙碱或细胞松弛素 D 破坏细胞骨架，在短暂暴露于低渗、等渗或高渗介质后对谷氨酰胺转运的影响（170， 分别为300和430 mosmol kg(-1)).3． GRGDTP 和 GRGESP 均不会显着影响基础谷氨酰胺摄取（0.05 mM；338 +/- 58 pmol min(-1)（毫克蛋白质）(-1)），但 GRGDTP 特异性地分别阻止低渗和高渗暴露引起的谷氨酰胺摄取增加 (71 %) 和减少 (39 %)。 4．秋水仙碱和细胞松弛素 D 可防止谷氨酰胺摄取随外部渗透压变化而增加或减少。他们还以渥曼青霉素敏感的方式将基础谷氨酰胺摄取量分别增加了 59 +/- 19 % 和 85 +/- 16 %。5．这些结果表明 ECM 整合素介导的细胞粘附和细胞骨架参与细胞体积变化的机械化学转导，以调节骨骼肌中谷氨酰胺转运的化学信号。磷脂酰肌醇 3-激酶可发挥维持机械传感器处于活性状态的作用。
1. Muscle glutamine transport is modulated in response to changes in cell volume by a mechanism dependent on active phosphatidylinositol 3-kinase. We investigated the possibility that this mechanism requires interactions between the extracellular matrix (ECM), integrins and the cytoskeleton as components of a mechanochemical transduction system.2. Using skeletal muscle cells, we studied effects of (a) inactivating integrin-substratum interactions by using integrin-binding peptide GRGDTP with inactive peptide GRGESP as control, and (b) disrupting the cytoskeleton using colchicine or cytochalasin D, on glutamine transport after brief exposure to hypo-osmotic, isosmotic or hyperosmotic medium (170, 300 and 430 mosmol kg(-1), respectively).3. Neither GRGDTP nor GRGESP significantly affected basal glutamine uptake (0.05 mM; 338 +/- 58 pmol min(-1) (mg protein)(-1)) but GRGDTP specifically prevented the increase (71 %) and decrease (39 %) in glutamine uptake in response to hypo- and hyperosmotic exposure, respectively.4. Colchicine and cytochalasin D prevented the increase and decrease in glutamine uptake in response to changes in external osmolality. They also increased basal glutamine uptake by 59 +/- 19 and 85 +/- 16 %, respectively, in a wortmannin-sensitive manner.5. These results indicate involvement of ECM-integrin-mediated cell adhesion and the cytoskeleton in mechanochemical transduction of cell volume changes to chemical signals modulating glutamine transport in skeletal muscle. Phosphatidylinositol 3-kinase may function to maintain the mechanotransducer in an active state.