Nervous system defects of AnkyrinB (-/-) mice suggest functional overlap between the cell adhesion molecule L1 and 440-kD AnkyrinB in premyelinated axons.
Nervous system defects of AnkyrinB (-/-) mice suggest functional overlap between the cell adhesion molecule L1 and 440-kD AnkyrinB in premyelinated axons.
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DOI：
10.1083/jcb.143.5.1305
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发表时间：
1998-11-30
期刊：
影响因子：
--
通讯作者：
Bennett V
中科院分区：
文献类型：
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作者：
Scotland P;Zhou D;Benveniste H;Bennett V
细胞粘附分子的L1 CAM家族和血影蛋白结合蛋白的锚蛋白家族是在脊椎动物和无脊椎动物的神经系统的不同背景中使用的跨细胞复合物中协作的候选者。这份报告提出的证据L1和440-kD的锚蛋白B在小鼠神经系统的有髓前轴突之间的功能耦合。L1和440-kD锚蛋白B在发育中的神经系统中共定位于有髓鞘的轴突束中，并且在髓鞘形成后都下调。AnklB（−/−）小鼠表现出与L1（−/−）小鼠相似但更严重的表型，并具有L1突变人类患者的特征。AnklymB（−/−）小鼠表现出胼胝体和锥体束发育不全、脑室扩张和视神经广泛变性，并在出生后21天死亡。AnklB（−/−）小鼠的长纤维束（包括大脑中的胼胝体、海马伞和内囊）以及脊髓的锥体束和侧柱的有髓鞘轴突中的L1减少。L1在出生后第1天的视神经中是明显的，但在突变小鼠中出生后第7天消失，而NCAM没有变化。ankleB（−/−）小鼠的视神经轴突变得扩张，直径比正常情况大8倍，并且在第20天退化。这些研究结果提供了第一个证据，在神经系统中的作用，并支持440 kD的锚蛋白B和L1之间的相互作用，这是必不可少的维持体内的有髓鞘轴突。
The L1 CAM family of cell adhesion molecules and the ankyrin family of spectrin-binding proteins are candidates to collaborate in transcellular complexes used in diverse contexts in nervous systems of vertebrates and invertebrates. This report presents evidence for functional coupling between L1 and 440-kD ankyrinB in premyelinated axons in the mouse nervous system. L1 and 440-kD ankyrinB are colocalized in premyelinated axon tracts in the developing nervous system and are both down-regulated after myelination. AnkyrinB (−/−) mice exhibit a phenotype similar to, but more severe, than L1 (−/−) mice and share features of human patients with L1 mutations. AnkyrinB (−/−) mice exhibit hypoplasia of the corpus callosum and pyramidal tracts, dilated ventricles, and extensive degeneration of the optic nerve, and they die by postnatal day 21. AnkyrinB (−/−) mice have reduced L1 in premyelinated axons of long fiber tracts, including the corpus callosum, fimbria, and internal capsule in the brain, and pyramidal tracts and lateral columns of the spinal cord. L1 was evident in the optic nerve at postnatal day 1 but disappeared by postnatal day 7 in mutant mice while NCAM was unchanged. Optic nerve axons of ankyrinB (−/−) mice become dilated with diameters up to eightfold greater than normal, and they degenerated by day 20. These findings provide the first evidence for a role of ankyrinB in the nervous system and support an interaction between 440-kD ankyrinB and L1 that is essential for maintenance of premyelinated axons in vivo.