Apical epidermal growth factor receptor signaling: Regulation of stretch-dependent exocytosis in bladder umbrella cells
Apical epidermal growth factor receptor signaling: Regulation of stretch-dependent exocytosis in bladder umbrella cells
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DOI：
10.1091/mbc.e06-09-0842
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发表时间：
2007-04-01
影响因子：
3.3
通讯作者：
Apodaca, Gerard
中科院分区：
文献类型：
--
作者：
Balestreire, Elena M.;Apodaca, Gerard
极化上皮细胞的顶面接受来自介质、生长因子和机械刺激的输入。这些刺激是如何协调来调节复杂的细胞功能，如极化膜交通尚不清楚。我们分析了伞细胞中生长因子信号传导和机械刺激的需求，伞细胞排列在膀胱粘膜表面，动态插入和去除顶膜以响应拉伸。我们观察到，拉伸刺激的胞吐作用需要顶端表皮生长因子（EGF）受体的激活和激活发生在肝素结合EGF样生长因子前体裂解下游的自分泌方式。顶端胞吐的长期变化依赖于蛋白质的合成，这发生在EGF受体依赖的促分裂原活化蛋白激酶信号转导的激活。我们的研究结果表明，一种新的生理作用，耦合上游机械刺激下游顶端表皮生长因子受体激活，可调节顶端表面积的变化，在膀胱充盈的表皮生长因子受体。
The apical surface of polarized epithelial cells receives input from mediators, growth factors, and mechanical stimuli. How these stimuli are coordinated to regulate complex cellular functions such as polarized membrane traffic is not understood. We analyzed the requirement for growth factor signaling and mechanical stimuli in umbrella cells, which line the mucosal surface of the bladder and dynamically insert and remove apical membrane in response to stretch. We observed that stretch-stimulated exocytosis required apical epidermal growth factor (EGF) receptor activation and that activation occurred in an autocrine manner downstream of heparin-binding EGF-like growth factor precursor cleavage. Long-term changes in apical exocytosis depended on protein synthesis, which occurred upon EGF receptor-dependent activation of mitogen-activated protein kinase signaling. Our results indicate a novel physiological role for the EGF receptor that couples upstream mechanical stimuli to downstream apical EGF receptor activation that may regulate apical surface area changes during bladder filling.