GAIP, GIPC and Gαi3 are concentrated in endocytic compartments of proximal tubule cells:: Putative role in regulating Megalin's function
GAIP, GIPC and Gαi3 are concentrated in endocytic compartments of proximal tubule cells:: Putative role in regulating Megalin's function
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DOI：
10.1681/asn.v134918
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发表时间：
2002-04-01
影响因子：
13.6
通讯作者：
Farquhar, MG
中科院分区：
文献类型：
--
作者：
Lou, XJ;Mcquistan, T;Farquhar, MG
巨蛋白是近端小管上皮细胞（PTE）中最丰富的内吞受体，它集中在刷状缘区域的网格蛋白包被的小凹（CCP）和小泡中。异源三聚体G蛋白α亚基Galpha 13也定位于PTE的刷状缘区域。通过免疫荧光，G蛋白介导的信号通路的组分GIPC和GAIP也集中在PTE的刷状缘区域，并且存在于表达巨蛋白的细胞系中。通过细胞分级，这些信号分子与巨蛋白共沉积在刷状缘和微绒毛组分中。GAIP通过免疫电子显微镜在CCP中发现，GIPC在CCP和肾刷状缘内吞隔室的顶端小管中发现。在沉淀测定中，GST-GIPC特异性结合巨蛋白。Galpha 13、GIPC和GAIP与巨蛋白在近端小管的内吞隔室中的浓度，其中发生广泛的内吞作用，以及GIPC和巨蛋白的胞质尾之间的相互作用表明了G蛋白介导的模型。信号传导可以调节巨蛋白的内吞功能和/或运输。
Megalin is the most abundant endocytic receptor in the proximal tubule epithelium (PTE), where it is concentrated in clathrin-coated pits (CCPs) and vesicles in the brush border region. The heterotrimeric G protein alpha subunit, Galphai3, has also been localized to the brush border region of PTE. By immunofluorescence GIPC and GAIP, components of G protein-mediated signaling pathways, are also concentrated in the brush border region of PTE and are present in megalin-expressing cell lines. By cell fractionation, these signaling molecules cosediment with megalin in brush border and microvillar fractions. GAIP is found by immunoelectron microscopy in CCPs, and GIPC is found in CCPs and apical tubules of endocytic compartments in the renal brush border. In precipitation assays, GST-GIPC specifically binds megalin. The concentration of Galphai3, GIPC, and GAIP with megalin in endocytic compartments of the proximal tubule, where extensive endocytosis occurs, and the interaction between GIPC and the cytoplasmic tail of megalin suggest a model whereby G protein-mediated. signaling may regulate megalin's endocytic function and/or trafficking.