Takeda Y, Asou H, Murakami Y, Miura M, Kobayashi M, Uyemura K
Department of Physiology, Keio University School of Medicine, Tokyo, Japan.
J Neurochem. 1996 Jun;66(6):2338-49. doi: 10.1046/j.1471-4159.1996.66062338.x.
The cell adhesion molecule L1 is a multifunctional protein in the nervous system characterizing cell adhesion, migration, and neurite outgrowth. In addition to full-length L1, we found an alternatively spliced variant lacking both the KGHHV sequence in the extracellular part and the RSLE sequence in the cytoplasmic part of L1. This L1 variant was expressed exclusively in nonneuronal cells such as Schwann cells, astrocytes, and oligodendrocytes, in contrast to the expression of the full-length L1 in neurons and cells of neuronal origin. To investigate the functions of the L1 variant, we established cell lines transfected with a cytoplasmic short L1 (L1cs) cDNA that lacks only the 12-bp segment encoding for the RSLE sequence. The promoting activities of homophilic cell adhesion, neurite outgrowth, and neuronal cell migration of L1cs-transfected cells (L4-2) were similar to those of full-length L1-transfected cells (L3-1), but the cell migratory activity of L4-2 itself was clearly lower than that of L3-1. In conclusion, the short form of L1 is a nonneuronal type, in contrast to the neuronal type of the full-length L1. Deletion of the four amino acids RSLE in the cytoplasmic region of L1 markedly reduced cell migratory activity, suggesting an importance of the RSLE sequence for the signaling events of neuronal migration mediated by L1.
细胞粘附分子L1是神经系统中的一种多功能蛋白，具有细胞粘附、迁移和神经突生长的特性。除全长L1外，我们还发现了一种选择性剪接变体，该变体在L1的细胞外部分缺少KGHHV序列，在细胞质部分缺少RSLE序列。与全长L1在神经元和神经源性细胞中的表达不同，这种L1变体仅在非神经元细胞如施万细胞、星形胶质细胞和少突胶质细胞中表达。为了研究L1变体的功能，我们建立了用细胞质短L1（L1cs）cDNA转染的细胞系，该cDNA仅缺少编码RSLE序列的12个碱基对片段。L1cs转染细胞（L4-2）的同源性细胞粘附、神经突生长和神经元细胞迁移的促进活性与全长L1转染细胞（L3-1）相似，但L4-2自身的细胞迁移活性明显低于L3-1。总之，与全长L1的神经元类型不同，L1的短形式是非神经元类型。L1细胞质区域中四个氨基酸RSLE的缺失显著降低了细胞迁移活性，表明RSLE序列对于L1介导的神经元迁移信号事件具有重要性。
