Upregulation and maintenance of gap junctional communication in lens cells.
Upregulation and maintenance of gap junctional communication in lens cells.
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DOI：
10.1016/j.exer.2008.11.031
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发表时间：
2009-05
影响因子：
3.4
通讯作者：
Musil, Linda S.
中科院分区：
文献类型：
--
作者：
Boswell, Bruce A.;Le, Anh-Chi N.;Musil, Linda S.
透镜的细胞通过由连接蛋白43、46和50组成的广泛的间隙连接细胞间通道网络连接。我们已经提出，并通过实验支持，假设成纤维细胞生长因子（FGF）信号是上调间隙连接介导的细胞间耦合（GJIC）在透镜赤道。FGF在培养的透镜细胞中增加GJIC的能力需要持续激活细胞外信号调节激酶（ERK）。在其他细胞类型中，ERK的激活已显示阻断由连接蛋白43（Cx43）介导的GJIC。为什么ERK信号传导不阻断透镜细胞偶联尚不清楚。透镜间隙连接调节中另一个未解决的问题是在成熟透镜纤维细胞中生物合成细胞器丧失之前合成的连接蛋白如何避免在无细胞器区形成期间降解。我们已经解决了这些问题，使用原代鸡胚透镜上皮细胞的无血清培养（称为DCDMLs）。我们表明，FGF刺激ERK在DCDMLs通过经典的Ras/Raf 1途径，和的原因，无论是基础或生长因子刺激的GJIC被阻断ERK的激活是因为它不是由Cx43介导的。在成纤维细胞中，Cx43在转运至质膜后的正常快速降解速率通过直接（ALLN;环氧霉素）或间接（砷化合物产生氧化性未折叠/错误折叠的蛋白质）阻止泛素/蛋白酶体系统（UPS）作用于其正常底物的处理而降低。我们在这里表明，Cx45.6和Cx 56，鸡的直系同源的哺乳动物Cx 50和Cx46，表现类似的DCDMLs。当细胞器在纤维细胞的成熟过程中裂解时，它们向细胞质中释放大量新蛋白质，这些蛋白质具有使UPS的容量饱和和/或损害UPS的功能的潜力。这将有助于在无细胞器区形成期间使间隙连接免于降解，从而尽管缺乏从头连接蛋白合成，但仍保留成熟纤维细胞之间的GJIC。
The cells of the lens are joined by an extensive network of gap junction intercellular channels consisting of connexins 43, 46, and 50. We have proposed, and experimentally supported, the hypothesis that fibroblast growth factor (FGF) signaling is required for upregulation of gap junction–mediated intercellular coupling (GJIC) at the lens equator. The ability of FGF to increase GJIC in cultured lens cells requires sustained activation of extracellular signal-regulated kinase (ERK). In other cell types, activation of ERK has been shown to block GJIC mediated by connexin43 (Cx43). Why ERK signaling does not block lens cell coupling is not known. Another unresolved issue in lens gap junction regulation is how connexins, synthesized before the loss of biosynthetic organelles in mature lens fiber cells, avoid degradation during formation of the organelle-free zone. We have addressed these questions using serum-free cultures (termed DCDMLs) of primary embryonic chick lens epithelial cells. We show that FGF stimulates ERK in DCDMLs via the canonical Ras/Raf1 pathway, and that the reason that neither basal or growth factor-stimulated GJIC is blocked by activation of ERK is because it is not mediated by Cx43. In fibroblastic cells, the normally rapid rate of degradation of Cx43 after its transport to the plasma membrane is reduced by treatments that either directly (ALLN; epoxomicin) or indirectly (generation of oxidatively un/mis-folded proteins by arsenic compounds) prevent the ubiquitin/proteasome system (UPS) from acting on its normal substrates. We show here that Cx45.6 and Cx56, the chick orthologs of mammalian Cx50 and Cx46, behave similarly in DCDMLs. When organelles lyse during the maturation of fiber cells, they release into the cytosol a large amount of new proteins that have the potential to saturate the capacity, and/or compromise the function, of the UPS. This would serve to spare gap junctions from degradation during formation of the organelle-free zone, thereby preserving GJIC between mature fiber cells despite the lack of de novo connexin synthesis.
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影响因子：
64.5
作者：
Gong, XH;Li, E;Gilula, NB
通讯作者：
Gilula, NB
影响因子：
4.4
作者：
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影响因子：
3.4
作者：
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通讯作者：
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影响因子：
3.3
作者：
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通讯作者：
Musil, Linda S.
影响因子：
4.8
作者：
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通讯作者：
CALOTHY, G