Castellani V, Chédotal A, Schachner M, Faivre-Sarrailh C, Rougon G
Laboratoire de Génétique et Physiologie du Développement, UMR 6545 CNRS, IBDM, Marseille, France.
Neuron. 2000 Aug;27(2):237-49. doi: 10.1016/s0896-6273(00)00033-7.
In humans, defects of the corticospinal tract have been attributed to mutations in the gene encoding L1 CAM, a phenotype that is reproduced in L1-deficient mice. Using coculture assays, we report that Sema3A secreted from the ventral spinal cord repels cortical axons from wild-type but not from L1-deficient mice. L1 and neuropilin-1 (NP-1) form a stable complex, and their extracellular domains can directly associate. Thus, L1 is a component of the Sema3A receptor complex, and L1 mutations may disrupt Sema3A signaling in the growth cone, leading to guidance errors. Addition of soluble L1Fc chimeric molecules does not restore Sema3A responsiveness of L1-deficient axons; instead, it converts the repulsion of wild-type axons into an attraction, further supporting a function for L1 in the Sema3A transducing pathways within the growth cone.
在人类中，皮质脊髓束缺陷被归因于编码L1细胞粘附分子（L1 CAM）的基因突变，这种表型在L1基因缺陷的小鼠中也会出现。通过共培养试验，我们发现从脊髓腹侧分泌的Sema3A排斥野生型小鼠的皮质轴突，但不排斥L1基因缺陷小鼠的皮质轴突。L1和神经纤毛蛋白-1（NP-1）形成稳定的复合物，它们的胞外结构域可以直接结合。因此，L1是Sema3A受体复合物的一个组成部分，L1突变可能会破坏生长锥中的Sema3A信号传导，导致导向错误。添加可溶性L1Fc嵌合分子并不能恢复L1基因缺陷轴突对Sema3A的反应；相反，它将野生型轴突的排斥转变为吸引，进一步支持了L1在生长锥内Sema3A转导途径中的作用。
