Semaphorin3A-induced receptor endocytosis during axon guidance responses is mediated by L1 CAM
Semaphorin3A-induced receptor endocytosis during axon guidance responses is mediated by L1 CAM
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DOI：
10.1016/j.mcn.2004.01.010
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发表时间：
2004-05-01
影响因子：
3.5
通讯作者：
Rougon, G
中科院分区：
文献类型：
--
作者：
Castellani, V;Falk, J;Rougon, G
在轴突导航过程中，Semaphorin3A 诱导的生长锥回缩与内吞作用相关。尽管其功能仍然难以捉摸，但我们之前表明，免疫球蛋白超家族 L1 的细胞粘附分子与受体复合物的 Sema3A 结合亚基 Neuropilin-1 (NP-1) 相关，并且是 Sema3A 引发轴突排斥反应所必需的。我们在此报告，在 Sema3A 与 NP-1 结合后，L1 和 NP-1 通过 L1 介导的网格蛋白依赖性机制共同内化。我们发现，在 COS7 细胞中，L1/NP-1 内吞作用与细胞收缩相关，类似于用 Plexin (Plex)/NP-1 或 Plex/NP1/L1 复合物观察到的细胞收缩。在神经元培养物中，L1 模拟肽能够将 Sema3A 排斥反应转变为吸引反应，从而阻止内吞作用和生长锥塌陷。同样，在 COS7 细胞模型中，肽应用可防止 Sema3 诱导的 L1/NP-1 内化和细胞崩溃。这些研究表明，L1/ NP-1 复合物能够在配体激活后通过 L1 介导受体内化，对 Sema3A 产生生物反应。他们还揭示了 L1/NP-1 顺式和反式相互作用控制的内吞作用在 Sema3A 介导的轴突引导中至关重要。 (C) 2004 Elsevier Inc. 保留所有权利。
During axon navigation, Semaphorin3A-induced growth cone retraction is correlated with endocytosis. Although its function remains elusive, we showed previously that the cell adhesion molecule of the immunoglobulin super family L1 associates with Neuropilin-1 (NP-1) the Sema3A-binding subunit of the receptor complex and is required for Sema3A to elicit axonal repulsive responses. We report here that upon Sema3A binding to NP-1, L1 and NP-1 are co-internalized through a clathrin-dependent mechanism mediated by L1. We show that in COS7 cells, L1/NP-1 endocytosis is correlated with a cell contraction similar to that observed with the Plexin (Plex)/NP-1 or Plex/NP1/L1 complexes. In neuronal cultures, a L1-mimetic peptide able to switch Sema3A repulsive responses to attraction blocks both endocytosis and growth cone collapse. Similarly, in the COS7 cell model, peptide application prevents both the Sema3-induced L1/NP-1 internalization and cell collapse. These studies demonstrate that the L1/ NP-1 complex is able to confer a biological response to Sema3A with L1 mediating receptor internalization following ligand activation. They also reveal that endocytosis controlled by L1/NP-1 cis and trans interactions is pivotal in Sema3A-mediated axon guidance. (C) 2004 Elsevier Inc. All rights reserved.