Ankyrin binding mediates L1CAM interactions with static components of the cytoskeleton and inhibits retrograde movement of L1CAM on the cell surface.

Ankyrin binding mediates L1CAM interactions with static components of the cytoskeleton and inhibits retrograde movement of L1CAM on the cell surface.
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DOI:
10.1083/jcb.200211011
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发表时间:
2003-08-18
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Felsenfeld DP
Felsenfeld DP
中科院分区:
其他
文献类型:
--
作者:
Gil OD;Sakurai T;Bradley AE;Fink MY;Cassella MR;Kuo JA;Felsenfeld DP

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黏附受体在细胞黏附和迁移中的作用主要依赖于与细胞骨架的相互作用。在细胞黏附过程中,细胞骨架相互作用稳定受体以加强黏附接触。相反,在细胞迁移过程中,黏附蛋白被认为与细胞骨架的动态成分相互作用,允许牵引力通过受体传递到细胞外环境。L1细胞黏附分子(L1CAM)是Ig超家族的成员之一,在神经元生长锥的迁移和相邻轴突之间的静态黏附中起着至关重要的作用。为了了解L1CAM在黏附和迁移中的作用基础,我们直接量化了L1CAM在ND-7神经母细胞瘤杂交细胞上表面的扩散特征,以此作为受体-细胞骨架相互作用的指标。我们发现细胞表面L1CAM参与了扩散、逆行和静止行为,这与L1CAM与两组细胞骨架蛋白之间的相互作用是一致的。我们提供的证据表明,细胞骨架接头蛋白ankyrin在抑制依赖肌动蛋白的L1CAM逆行运动的同时,介导了静止行为。此外,L1CAM-Ankyrin相互作用的抑制剂促进了L1CAM介导的轴突生长。综上所述,这些结果表明,锚蛋白结合在L1CAM介导的黏附和迁移的反协调调节中起着至关重要的作用。
The function of adhesion receptors in both cell adhesion and migration depends critically on interactions with the cytoskeleton. During cell adhesion, cytoskeletal interactions stabilize receptors to strengthen adhesive contacts. In contrast, during cell migration, adhesion proteins are believed to interact with dynamic components of the cytoskeleton, permitting the transmission of traction forces through the receptor to the extracellular environment. The L1 cell adhesion molecule (L1CAM), a member of the Ig superfamily, plays a crucial role in both the migration of neuronal growth cones and the static adhesion between neighboring axons. To understand the basis of L1CAM function in adhesion and migration, we quantified directly the diffusion characteristics of L1CAM on the upper surface of ND-7 neuroblastoma hybrid cells as an indication of receptor–cytoskeleton interactions. We find that cell surface L1CAM engages in diffusion, retrograde movement, and stationary behavior, consistent with interactions between L1CAM and two populations of cytoskeleton proteins. We provide evidence that the cytoskeletal adaptor protein ankyrin mediates stationary behavior while inhibiting the actin-dependent retrograde movement of L1CAM. Moreover, inhibitors of L1CAM–ankyrin interactions promote L1CAM-mediated axon growth. Together, these results suggest that ankyrin binding plays a crucial role in the anti-coordinate regulation of L1CAM-mediated adhesion and migration.
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