THE NEURONAL CELL-SURFACE MOLECULE MITOGENIC FOR SCHWANN-CELLS IS A HEPARIN-BINDING PROTEIN
THE NEURONAL CELL-SURFACE MOLECULE MITOGENIC FOR SCHWANN-CELLS IS A HEPARIN-BINDING PROTEIN
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DOI：
10.1073/pnas.85.18.6992
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发表时间：
1988-09-01
影响因子：
11.1
通讯作者：
GLASER, L
中科院分区：
文献类型：
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作者：
RATNER, N;HONG, D;GLASER, L
细胞表面的胚胎外周神经元为雪旺细胞提供促有丝分裂刺激。我们报告（i）这种促有丝分裂活性的溶解从大鼠背根神经节神经元生长在组织培养和（ii）的溶解和部分纯化的促有丝分裂活性从新生大鼠大脑。提取的促有丝分裂活性是外周的而不是膜固有的，提取后稳定，并且在不存在血清的情况下具有促有丝分裂活性（定义神经元促有丝分裂的最严格标准）。我们以前提供的证据表明，神经元细胞表面硫酸乙酰肝素蛋白聚糖是神经元有丝分裂活性表达所必需的。我们现在表明，促有丝分裂活性可以从蛋白聚糖分离的膜中提取，通过其与固定化肝素结合的能力进行测定。解离后，低浓度的肝素（1 μ g/ml）抑制有丝分裂原刺激许旺细胞分裂的能力。碱性成纤维细胞生长因子（FGF）对许旺细胞有弱的促有丝分裂作用，但在促有丝分裂脑提取物中不存在（基于免疫印迹）。用FGF特异性抗体进行的免疫耗竭实验表明，从神经元中提取的促有丝分裂活性不是这种肝素结合有丝分裂原的一种形式。酸性FGF对许旺细胞不具有促有丝分裂作用，并且不存在于促有丝分裂脑提取物中。我们认为，这些和以前的数据表明，轴突有丝分裂原是一种蛋白多糖-生长因子复合物，限制促有丝分裂活性的轴突表面，保护有丝分裂原对其他蛋白多糖失活，并提供有效的介绍有丝分裂原的雪旺细胞。
The cell surface embryonic peripheral neurons provides a mitogenic stimulus for Schwann cells. We report (i) the solubilization of this mitogenic activity from rat dorsal root ganglion neurons grown in tissue culture and (ii) the solubilization and partial purification of mitogenic activity from neonatal rat brains. Extracted mitogenic activity is peripheral rather than intrinsic to the membrane, stable after extraction, and active as a mitogenic in the absence of serum (the most stringent criterion defining the neuronal mitogenic). We have previously provided evidence suggesting that a neuronal cell-surface heparan sulfate proteoglycan is required for expression of the neurons'' mitogenic activity. We now show that mitogenic activity can be extracted from the membrane dissciated from proteoglycan as assayed by its ability to bind to immobilized heparin. After dissociation, low concentrations of heparin (I .mu.g/ml) inhibit the ability of the mitogen to stimulate Schwann cell division. Basic fibroblast growth factor (FGF) is weakly mitogenic for Schwann cells, but it is not present in mitogenic brain extracts (based on immunoblotting). Immunodepletion experiments with specific antibodies to FGF indicate that the mitogenic activity extracted from neurons is not a form of this heparin-binding mitogen. Acidic FGF is not mitogenic for Schwann cells and is not present in mitogenic brain extracts. We suggest that these and previous data indicate the neurite mitogen is a proteoglycan-growth factor complex that limits mitogenic activity to the axonal surface, protects mitogen against inactivation by other proteoglycans, and provides for effective presentation of mitogen to the Schwann cell.