A novel role for FGF and extracellular signal-regulated kinase in gap junction-mediated intercellular communication in the lens.
A novel role for FGF and extracellular signal-regulated kinase in gap junction-mediated intercellular communication in the lens.
复制标题
FGF和细胞外信号调节激酶在透镜中的细胞间通信中的新作用。
DOI：
10.1083/jcb.200101057
复制
发表时间：
2001-07-09
影响因子：
7.8
通讯作者：
Musil, L S
中科院分区：
文献类型：
--
作者：
Le, A C;Musil, L S
间隙连接介导的细胞间耦合在透镜的赤道区域比在任一极高，这一特性被认为是透镜透明度所必需的。我们发现，成纤维细胞生长因子（FGF）上调间隙连接细胞间染料转移在原代培养的鸡胚透镜细胞没有检测到增加间隙连接蛋白（连接蛋白）的合成或组装。在诱导透镜细胞分化方面与FGF一样有效的胰岛素和胰岛素样生长因子1对缝隙连接没有影响。FGF诱导透镜细胞中细胞外信号调节激酶（ERK）的持续激活，这是增加间隙连接偶联所必需和充分的事件。我们还确定了玻璃体液作为体内来源的FGF样细胞间通讯促进活动，并表明，FGF诱导的ERK激活在完整的透镜是更高的赤道区比在极性和核心纤维。这些发现支持了一个模型，其中通过ERK途径的FGF信号传导的区域差异导致适当的透镜功能所需的缝隙连接偶联的不对称性。我们的研究结果还确定上调细胞间通讯作为一个新的功能，持续ERK激活和改变目前的范式，ERK只负调节间隙连接通道的活性。
Gap junction–mediated intercellular coupling is higher in the equatorial region of the lens than at either pole, a property believed to be essential for lens transparency. We show that fibroblast growth factor (FGF) upregulates gap junctional intercellular dye transfer in primary cultures of embryonic chick lens cells without detectably increasing either gap junction protein (connexin) synthesis or assembly. Insulin and insulin-like growth factor 1, as potent as FGF in inducing lens cell differentiation, had no effect on gap junctions. FGF induced sustained activation of extracellular signal–regulated kinase (ERK) in lens cells, an event necessary and sufficient to increase gap junctional coupling. We also identify vitreous humor as an in vivo source of an FGF-like intercellular communication-promoting activity and show that FGF-induced ERK activation in the intact lens is higher in the equatorial region than in polar and core fibers. These findings support a model in which regional differences in FGF signaling through the ERK pathway lead to the asymmetry in gap junctional coupling required for proper lens function. Our results also identify upregulation of intercellular communication as a new function for sustained ERK activation and change the current paradigm that ERKs only negatively regulate gap junction channel activity.