Basement membrane assembly of the integrin α8β1 ligand nephronectin requires Fraser syndrome-associated proteins.
Basement membrane assembly of the integrin α8β1 ligand nephronectin requires Fraser syndrome-associated proteins.
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DOI：
10.1083/jcb.201203065
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发表时间：
2012-05-28
期刊：
影响因子：
--
通讯作者：
Sekiguchi K
中科院分区：
文献类型：
--
作者：
Kiyozumi D;Takeichi M;Nakano I;Sato Y;Fukuda T;Sekiguchi K
QBRICK通过调节肾连蛋白的基底膜组装促进细胞与基底膜的整合素α8β1依赖性相互作用。基底膜蛋白质QBRICK的功能障碍引起弗雷泽综合征，其通过未知的机制导致肾畸形、隐眼、并指和营养不良性大疱性表皮细胞。在这里，我们发现整合素α8β1与基底膜的结合在Qbrick敲除小鼠中显著受损。这种受损的整联蛋白α8β1结合不是QBRICK丢失的直接结果，QBRICK本身是整联蛋白α8β1的配体，因为在QBRICK整联蛋白结合位点具有突变的敲入小鼠发育正常，并且在整联蛋白α8β1结合中没有表现出任何缺陷。相反，QBRICK的缺失显著降低了肾连蛋白的表达，肾连蛋白是肾脏发育所必需的整合素α8β1配体。在体内，肾连蛋白与QBRICK相关，并定位于致密层下区域，QBRICK也位于该区域。总的来说，这些发现表明QBRICK通过调节肾连蛋白的基底膜组装促进细胞与基底膜的整合素α8β1依赖性相互作用，并解释了为什么弗雷泽综合征中发生肾功能缺陷。
QBRICK facilitates the integrin α8β1–dependent interactions of cells with basement membranes by regulating the basement membrane assembly of nephronectin. Dysfunction of the basement membrane protein QBRICK provokes Fraser syndrome, which results in renal dysmorphogenesis, cryptophthalmos, syndactyly, and dystrophic epidermolysis bullosa through unknown mechanisms. Here, we show that integrin α8β1 binding to basement membranes was significantly impaired in Qbrick-null mice. This impaired integrin α8β1 binding was not a direct consequence of the loss of QBRICK, which itself is a ligand of integrin α8β1, because knock-in mice with a mutation in the integrin-binding site of QBRICK developed normally and do not exhibit any defects in integrin α8β1 binding. Instead, the loss of QBRICK significantly diminished the expression of nephronectin, an integrin α8β1 ligand necessary for renal development. In vivo, nephronectin associated with QBRICK and localized at the sublamina densa region, where QBRICK was also located. Collectively, these findings indicate that QBRICK facilitates the integrin α8β1–dependent interactions of cells with basement membranes by regulating the basement membrane assembly of nephronectin and explain why renal defects occur in Fraser syndrome.
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影响因子：
3.5
作者：
Pitera JE;Scambler PJ;Woolf AS
通讯作者：
Woolf AS
影响因子：
64.5
作者：
Fujiwara H;Ferreira M;Donati G;Marciano DK;Linton JM;Sato Y;Hartner A;Sekiguchi K;Reichardt LF;Watt FM
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Watt FM
影响因子：
64.8
作者：
Moore, MW;Klein, RD;Rosenthal, A
通讯作者：
Rosenthal, A
影响因子：
4.8
作者：
Ido, Hiroyuki;Nakamura, Aya;Sekiguchi, Kiyotoshi
通讯作者：
Sekiguchi, Kiyotoshi
DOI：
10.1073/pnas.092130099
发表时间：
2002-05-14
影响因子：
11.1
作者：
Bladt, F;Tafuri, A;Pawson, T
通讯作者：
Pawson, T