Megalin is a receptor for albumin in astrocytes and is required for the synthesis of the neurotrophic factor oleic acid
Megalin is a receptor for albumin in astrocytes and is required for the synthesis of the neurotrophic factor oleic acid
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DOI：
10.1111/j.1471-4159.2008.05462.x
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发表时间：
2008-08-01
影响因子：
4.7
通讯作者：
Medina, Jose M.
中科院分区：
文献类型：
--
作者：
Bento-Abreu, Andre;Velasco, Ana;Medina, Jose M.
我们以前已经表明，星形胶质细胞中白蛋白的摄取和转胞吞促进神经营养因子油酸的合成。虽然白蛋白诱导油酸合成的机制是众所周知的，但星形胶质细胞中白蛋白摄取的机制仍然未知。在这项工作中，我们发现星形胶质细胞表达巨蛋白，一种包括白蛋白在内的多种配体的内吞受体。此外，当巨蛋白的活性被特异性抗体阻断或通过用特异性siRNA沉默巨蛋白而被阻断时，白蛋白结合和内化强烈降低，表明巨蛋白是星形胶质细胞中白蛋白结合和内化所需的。由于星形胶质细胞摄取白蛋白的目的是合成神经营养因子油酸，我们测试了巨蛋白沉默的星形胶质细胞在白蛋白存在下合成和释放油酸的能力。我们的研究结果表明，在巨蛋白沉默的星形胶质细胞的细胞外介质中发现的油酸的量强烈减少，与他们的控制。总之，这项工作的结果表明，巨蛋白是星形胶质细胞中白蛋白的受体，是合成神经营养因子油酸所必需的。因此，建议白蛋白可能参与在巨蛋白缺陷小鼠中观察到的前脑无裂综合征。
We have previously shown that the uptake and transcytosis of albumin in astrocytes promote the synthesis of the neurotrophic factor oleic acid. Although the mechanism by which albumin induces oleic acid synthesis is well known, the mechanism of albumin uptake in astrocytes remains unknown. In this work, we found that astrocytes express megalin, an endocytic receptor for multiple ligands including albumin. In addition, when the activity of megalin is blocked by specific antibodies or by silencing megalin with specific siRNA, albumin binding and internalization is strongly reduced indicating that megalin is required for albumin binding and internalization in the astrocyte. Since the uptake of albumin in astrocytes aims at synthesizing the neurotrophic factor oleic acid, we tested the ability of megalin-silenced astrocytes to synthesize and release oleic acid in the presence of albumin. Our results showed that the amount of oleic acid found in the extracellular medium of megalin-silenced astrocytes was strongly reduced as compared with their controls. Together, the results of this work indicate that megalin is a receptor for albumin in astrocytes and is required for the synthesis of the neurotrophic factor oleic acid. Consequently, the possible involvement of albumin in the holoprosencephalic syndrome observed in megalin-deficient mice is suggested.