N-sulfation of heparan sulfate is critical for syndecan-4-mediated podocyte cell-matrix interactions.
N-sulfation of heparan sulfate is critical for syndecan-4-mediated podocyte cell-matrix interactions.
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硫酸乙酰肝素的 N-硫酸化对于 syndecan-4 介导的足细胞细胞-基质相互作用至关重要。
DOI：
10.1152/ajprenal.00603.2015
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
McCarthy,KevinJ
中科院分区：
文献类型：
--
作者：
Sugar,Terrel;Wassenhove-McCarthy,DeborahJ;Orr,AWayne;Green,Jonette;vanKuppevelt,ToinH;McCarthy,KevinJ
先前的研究表明，足细胞不能在细胞表面蛋白聚糖核心蛋白上组装硫酸乙酰肝素，从而损害了细胞-基质相互作用。本报告进一步探讨了完整乙酰肝素链的N-硫酸化在足细胞-基质相互作用中的作用。为了本研究的目的，开发了一种小鼠模型，其中酶N-脱乙酰基酶/N-磺基转移酶1（NDST 1）在足细胞和缺乏NDST 1的永生化足细胞系中特异性缺失，并用于探索这种突变对体外足细胞行为的影响。NDST 1是一种双功能酶，最终负责细胞产生的乙酰肝素糖胺聚糖的N-硫酸化。与对照组相比，足细胞无Ndst 1（Ndst 1 −/−）的小鼠肾小球的免疫染色显示细胞表面蛋白聚糖、syndecan-4和α-actinin-4的定位模式被破坏。突触足蛋白和nephrin的免疫染色模式没有显示出显著的变化。体外研究表明，Ndst 1 −/−足细胞附着、扩散和迁移的效率低于Ndst 1 +/+足细胞。对参与细胞-基质相互作用的分子的几种标记物进行体外免疫染色显示，Ndst 1 −/−细胞减少了syndecan-4的聚集，减少了蛋白激酶C α、α-辅肌动蛋白-4、粘着斑蛋白和磷酸化粘着斑激酶向粘着斑的募集。与Ndst 1 +/+细胞相比，Ndst 1 −/−细胞内磷酸化粘着斑激酶的总量减少。与Ndst 1 +/+细胞相比，Ndst 1 −/−细胞表面活化整合素α5β1的丰度显著降低。这些结果突出了硫酸乙酰肝素N-硫酸化在促进正常足细胞-基质相互作用中的关键作用。
Previous research has shown that podocytes unable to assemble heparan sulfate on cell surface proteoglycan core proteins have compromised cell-matrix interactions. This report further explores the role ofN-sulfation of intact heparan chains in podocyte-matrix interactions. For the purposes of this study, a murine model in which the enzymeN-deacetylase/N-sulfotransferase 1 (NDST1) was specifically deleted in podocytes and immortalized podocyte cell lines lacking NDST1 were developed and used to explore the effects of such a mutation on podocyte behavior in vitro. NDST1 is a bifunctional enzyme, ultimately responsible forN-sulfation of heparan glycosaminoglycans produced by cells. Immunostaining of glomeruli from mice whose podocytes were null forNdst1(Ndst1−/−) showed a disrupted pattern of localization for the cell surface proteoglycan, syndecan-4, and for α-actinin-4 compared with controls. The pattern of immunostaining for synaptopodin and nephrin did not show as significant alterations. In vitro studies showed thatNdst1−/−podocytes attached, spread, and migrated less efficiently thanNdst1+/+podocytes. Immunostaining in vitro for several markers for molecules involved in cell-matrix interactions showed thatNdst1−/−cells had decreased clustering of syndecan-4 and decreased recruitment of protein kinase-Cα, α-actinin-4, vinculin, and phospho-focal adhesion kinase to focal adhesions. Total intracellular phospho-focal adhesion kinase was decreased inNdst1−/−compared withNdst1+/+cells. A significant decrease in the abundance of activated integrin α5β1 on the cell surface ofNdst1−/−cells compared withNdst1+/+cells was observed. These results serve to highlight the critical role of heparan sulfateN-sulfation in facilitating normal podocyte-matrix interactions.
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糖尿病大鼠肾小球氨基葡萄糖N-脱乙酰酶的抑制。
影响因子：
19.6
作者：
A. Kofoed‐Enevoldsen
通讯作者：
A. Kofoed‐Enevoldsen
Syndecan-4 核心蛋白足以组装粘着斑和肌动蛋白应力纤维。
影响因子：
4
作者：
Echtermeyer,F;Baciu,PC;Saoncella,S;Ge,Y;Goetinck,PF
通讯作者：
Goetinck,PF
Syndecan 4 硫酸乙酰肝素蛋白多糖是一种选择性富集且广泛分布的粘着斑成分。
影响因子：
3.3
作者：
Woods,A;Couchman,JR
通讯作者：
Couchman,JR
影响因子：
3.3
作者：
Orr, A. W.;Ginsberg, M. H.;Schwartz, M. A.
通讯作者：
Schwartz, M. A.
DOI：
10.1016/s0074-7696(01)07004-8
发表时间：
2001
期刊：
International review of cytology
影响因子：
--
作者：
J. Couchman;Ligong Chen;A. Woods
通讯作者：
J. Couchman;Ligong Chen;A. Woods