Cowan C A, Yokoyama N, Bianchi L M, Henkemeyer M, Fritzsch B
Center for Developmental Biology, University of Texas, Southwestern Medical Center, Dallas 75235, USA.
Neuron. 2000 May;26(2):417-30. doi: 10.1016/s0896-6273(00)81174-5.
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.
缺乏EphB2受体酪氨酸激酶的小鼠表现出一种细胞自主性、品系特异性的转圈行为，这种行为与前庭表型有关。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路径选择，而在成年突变体中，半规管内充满内淋巴的管腔严重缩小。EphB2在内耳上皮中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。通过证明与EphB2和B-ephrin的C末端结合的含PDZ结构域的蛋白质也能识别阴离子交换体和水通道蛋白的细胞质尾巴，提供了与液体调节的分子联系。这表明EphB2可能通过与运输氯离子、碳酸氢根离子和水的膜通道形成大分子结合来调节离子稳态和内淋巴液生成。
