EphB2 guides axons at the midline and is necessary for normal vestibular function
EphB2 guides axons at the midline and is necessary for normal vestibular function
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DOI：
10.1016/s0896-6273(00)81174-5
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发表时间：
2000-05-01
期刊：
影响因子：
16.2
通讯作者：
Fritzsch, B
中科院分区：
文献类型：
--
作者：
Cowan, CA;Yokoyama, N;Fritzsch, B
缺乏EphB 2受体酪氨酸激酶的小鼠表现出与前庭表型相关的细胞自主、菌株特异性的盘旋行为。在突变胚胎中，对侧内耳传出生长锥在中线处表现出不适当的通路选择，而在突变成人中，半规管的内淋巴填充腔严重减少。EphB 2在内耳上皮中的产生内淋巴的暗细胞中表达，并且这些细胞在突变体中显示出超微结构缺陷。通过证明结合EphB 2和B-肝配蛋白的C末端的含PDZ结构域的蛋白质也可以识别阴离子交换剂和水通道蛋白的细胞质尾部，提供了与流体调节的分子联系。这表明EphB 2可以通过与转运氯化物、碳酸氢盐和水的膜通道的大分子缔合来调节离子稳态和内淋巴液产生。
Mice lacking the EphB2 receptor tyrosine kinase display a cell-autonomous, strain-specific circling behavior that is associated with vestibular phenotypes. In mutant embryos, the contralateral inner ear efferent growth cones exhibit inappropriate pathway selection at the midline, while in mutant adults, the endolymph-filled lumen of the semicircular canals is severely reduced. EphB2 is expressed in the endolymph-producing dark cells in the inner ear epithelium, and these cells show ultrastructural defects in the mutants. A molecular link to fluid regulation is provided by demonstrating that PDZ domain-containing proteins that bind the C termini of EphB2 and B-ephrins can also recognize the cytoplasmic tails of anion exchangers and aquaporins. This suggests EphB2 may regulate ionic homeostasis and endolymph fluid production through macromolecular associations with membrane channels that transport chloride, bicarbonate, and water.