Syntaxin 16 regulates lumen formation during epithelial morphogenesis.
Syntaxin 16 regulates lumen formation during epithelial morphogenesis.
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DOI：
10.1371/journal.pone.0061857
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Choudhury A
中科院分区：
文献类型：
--
作者：
Jung JJ;Inamdar SM;Tiwari A;Ye D;Lin F;Choudhury A
在生理和病理条件下，细胞间连接的形成和维持都需要连接蛋白的靶向和运输。突触融合蛋白（Stx）家族的蛋白定位于各种亚细胞膜，并通过调节这些位点的囊泡融合事件来促进货物的细胞内转运。与质膜定位的Stx不同，内体和高尔基体定位的Stx蛋白在上皮形态发生中的作用还不太清楚。在这里，我们表明，Stx 16-内体和高尔基体定位的靶膜可溶性N-乙基马来酰亚胺附着蛋白受体（t-SNARE），在这些隔间之间的膜运输中发挥作用-是至关重要的管腔发育。在培养的Madin达比犬肾（MDCK）细胞中，Stx 16选择性上调，因为稀疏铺板的细胞达到汇合。Stx 16耗尽汇合单层一致显示出较低的跨上皮阻力比对照单层，并未能维持内源性和异位表达的E-钙粘蛋白在adherens交界处，由于减少再循环。我们进一步发现，尽管由在Matrigel中培养的MDCK细胞形成的囊肿具有单个中空腔，但由于有丝分裂纺锤体的异常定向，由stx 16耗尽的对应物形成的囊肿具有多个腔。最后，通过我们对表达claudinB：lynGFP转基因的斑马鱼的前肾管发育的分析，表明了stx 16在体内功能的类似作用;在该结构中（在stx 16-morphant胚胎中）缺乏stx 16功能导致了具有多于一个管腔的扩大的、扭曲的前肾管的发育。总之，我们的体外和体内研究确立了Stx 16在维持细胞-细胞连接的完整性中的作用，从而在肾上皮管腔的形态发生中发挥作用。
The formation and maintenance of cell-cell junctions, both under physiological and pathological conditions, requires the targeting and trafficking of junctional proteins. Proteins of the syntaxin (Stx)-family localize to a variety of subcellular membranes and contribute to intracellular transport of cargo by regulating vesicle fusion events at these sites. Unlike plasma membrane localized Stxs, the roles of endosome- and Golgi-localized stx proteins in epithelial morphogenesis are less understood. Here we show that Stx16– an endosome- and Golgi-localized target-membrane soluble N-ethylmaleimide attachment protein receptor (t-SNARE) that plays a role in membrane trafficking between these compartments – is essential for lumen development. In cultured Madin Darby Canine Kidney (MDCK) cells, Stx16 was selectively upregulated as sparsely plated cells attained confluency. Stx16-depleted confluent monolayers consistently showed lower transepithelial resistance than control monolayers, and failed to maintain endogenous and ectopically expressed E-cadherin at the adherens junctions due to decreased recycling. We further found that whereas cysts formed by MDCK cells cultured in Matrigel have a single hollow lumen, those formed by stx16-depleted counterparts had multiple lumens, due to abnormal orientiation of the mitotic spindle. Finally, a similar role for stx16 function in vivo is indicated by our analysis of pronephric-duct development in zebrafish expressing the claudinB:lynGFP transgene; lack of stx16 function in this structure (in stx16-morphant embryos) led to the development of enlarged, torturous pronephric ducts with more than one lumen. Taken together, our in vitro and in vivo studies establish a role for Stx16 in maintaining the integrity of cell-cell junctions, and thereby in morphogenesis of the kidney epithelial lumen.
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DOI：
10.1083/jcb.201009141
发表时间：
2011-03-21
期刊：
The Journal of cell biology
影响因子：
--
作者：
Baum B;Georgiou M
通讯作者：
Georgiou M
影响因子：
2.6
作者：
Horsfield, J;Ramachandran, A;Crosier, P
通讯作者：
Crosier, P
影响因子：
4
作者：
Bryant, David M.;Kerr, Markus C.;Stow, Jennifer L.
通讯作者：
Stow, Jennifer L.
影响因子：
4.8
作者：
Gee, Heon Yung;Tang, Bor Luen;Lee, Min Goo
通讯作者：
Lee, Min Goo
语法16和语法5是有效地逆行几种外源和内源性货物蛋白的逆行运输所必需的。
影响因子：
4
作者：
通讯作者：
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