NERVE GROWTH-FACTOR AND ITS LOW-AFFINITY RECEPTOR PROMOTE SCHWANN-CELL MIGRATION
NERVE GROWTH-FACTOR AND ITS LOW-AFFINITY RECEPTOR PROMOTE SCHWANN-CELL MIGRATION
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DOI：
10.1073/pnas.91.7.2795
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发表时间：
1994-03-29
影响因子：
11.1
通讯作者：
MATTHEW, WD
中科院分区：
文献类型：
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作者：
ANTON, ES;WESKAMP, G;MATTHEW, WD
已知在发育或再生的外周神经中迁移的雪旺细胞表达显著增加的神经生长因子（NGF）和低亲和力NGF受体（LNGFR）水平。雪旺氏细胞不表达可检测的pp 140 trk，这是神经元对神经生长因子的反应所必需的神经生长因子激活受体酪氨酸激酶。在雪旺细胞中观察到的迁移与NGF和LNGFR表达增强之间的时间相关性表明，NGF和LNGFR可能促进雪旺细胞迁移。为了测试这种可能性，我们研究了神经生长因子对雪旺细胞迁移的影响，在生物学相关的神经生长因子-穷人和神经生长因子-丰富的基板-正常或失神经周围（坐骨）神经，未经处理或预处理的神经生长因子的冷冻切片。结果表明，雪旺细胞在失神经支配的坐骨神经上迁移速度比在正常坐骨神经上快。NGF或LNGFR的抗体强烈但不完全地抑制去神经支配的神经上增强的迁移。用NGF预处理失神经节段进一步增加雪旺细胞迁移的速率。抗NGF或抗LNGFR的相同抗体消除了这种反应。这些结果表明，已知存在于胚胎和再生周围神经中的升高水平的NGF的一个功能是促进雪旺细胞的迁移。与神经元相反，pp 140 trk似乎是功能关键的NGF受体，雪旺细胞中的NGF反应依赖于LNGFR。
Migrating Schwann cells in developing or regenerating peripheral nerves are known to express dramatically increased levels of nerve growth factor (NGF) and the low-affinity NGF receptor (LNGFR). Schwann cells do not express detectable pp140trk, the NGF-activated receptor tyrosine kinase which is essential for neuronal responses to NGF. The temporal correlation observed in Schwann cells between migration and the enhanced expression of NGF and LNGFR suggests that NGF and LNGFR may promote Schwann cell migration. To test this possibility, we examined the effects of NGF on Schwann cell migration on cryostat sections of biologically relevant NGF-poor and NGF-rich substrates-normal or denervated peripheral (sciatic) nerve, untreated or pretreated with NGF. Results show that Schwann cells migrate more rapidly on denervated than on normal sciatic nerve. Antibodies to NGF or to LNGFR strongly, but incompletely, inhibit enhanced migration on denervated nerves. Pretreatment of denervated nerve sections with NGF increases further the rate of Schwann cell migration. The same antibodies to NGF or to LNGFR abolish this response. These results suggest that one function of the elevated levels of NGF known to be present in embryonic and regenerating peripheral nerves is to promote the migration of Schwann cells. In contrast to neurons, where pp140trk appears to be the functionally critical NGF receptor, NGF responses in Schwann cells depend on LNGFR.