Autosomal recessive polycystic kidney disease epithelial cell model reveals multiple basolateral epidermal growth factor receptor sorting pathways.
Autosomal recessive polycystic kidney disease epithelial cell model reveals multiple basolateral epidermal growth factor receptor sorting pathways.
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DOI：
10.1091/mbc.e09-12-1059
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发表时间：
2010-08-01
影响因子：
3.3
通讯作者：
Carlin CR
中科院分区：
文献类型：
--
作者：
Ryan S;Verghese S;Cianciola NL;Cotton CU;Carlin CR
我们发现多个基底外侧途径介导肾上皮细胞中EGF受体的分选。BPK小鼠模型中的多囊肾病等位基因Bicc 1干扰一种特异性EGF受体途径，导致受体的非极性递送，而不影响整体细胞极性。在多囊肾疾病中，肾上皮细胞基底外侧表面上EGF受体的分选和维持受到干扰，并且受体的顶端表达有助于疾病的严重程度。这些研究的目的是了解EGF受体错配的分子基础，使用成熟的常染色体隐性遗传疾病小鼠模型。我们已经发现，多种基底外侧通路介导肾上皮细胞中的EGF受体分选。该模型中的多囊肾病等位基因Bicc 1干扰一种特异性EGF受体途径，而不影响整体细胞极性。此外，其中一个途径是由一个潜在的基底外侧分选信号，恢复表皮生长因子受体的极性在囊性肾上皮细胞通过Rab 11阳性subapical室。这些研究为重建EGF受体极性和功能以抑制疾病进展的可能疗法提供了新的见解。他们还首次表明，在这些研究中使用的小鼠模型中有缺陷的Bicc 1基因调节上皮细胞特异性网格蛋白衔接子AP-1B介导的货物特异性蛋白分选。
We have discovered that multiple basolateral pathways mediate EGF receptor sorting in renal epithelial cells. The polycystic kidney disease allele in the BPK mouse model, Bicc1, interferes with one specific EGF receptor pathway, causing nonpolar delivery of the receptor without affecting overall cell polarity. Sorting and maintenance of the EGF receptor on the basolateral surface of renal epithelial cells is perturbed in polycystic kidney disease and apical expression of receptors contributes to severity of disease. The goal of these studies was to understand the molecular basis for EGF receptor missorting using a well-established mouse model for the autosomal recessive form of the disease. We have discovered that multiple basolateral pathways mediate EGF receptor sorting in renal epithelial cells. The polycystic kidney disease allele in this model, Bicc1, interferes with one specific EGF receptor pathway without affecting overall cell polarity. Furthermore one of the pathways is regulated by a latent basolateral sorting signal that restores EGF receptor polarity in cystic renal epithelial cells via passage through a Rab11-positive subapical compartment. These studies give new insights to possible therapies to reconstitute EGF receptor polarity and function in order to curb disease progression. They also indicate for the first time that the Bicc1 gene that is defective in the mouse model used in these studies regulates cargo-specific protein sorting mediated by the epithelial cell specific clathrin adaptor AP-1B.
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DOI：
10.1523/jneurosci.3907-09.2009
发表时间：
2009-10-21
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Dupraz S;Grassi D;Bernis ME;Sosa L;Bisbal M;Gastaldi L;Jausoro I;Cáceres A;Pfenninger KH;Quiroga S
通讯作者：
Quiroga S
影响因子：
64.5
作者：
Fölsch, H;Ohno, H;Mellman, I
通讯作者：
Mellman, I
影响因子：
19.6
作者：
Brown, NE;Murcia, NS
通讯作者：
Murcia, NS
影响因子：
5.3
作者：
CARLIN, CR;KNOWLES, BB
通讯作者：
KNOWLES, BB
影响因子：
2.5
作者：
Cogswell, C;Price, SJ;Bryda, EC
通讯作者：
Bryda, EC