Tmod3 regulates polarized epithelial cell morphology
Tmod3 regulates polarized epithelial cell morphology
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DOI：
10.1242/jcs.011445
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发表时间：
2007-10-15
影响因子：
4
通讯作者：
Fowler, Velia M.
中科院分区：
文献类型：
--
作者：
Weber, Kari L.;Fischer, Robert S.;Fowler, Velia M.
虽然肌动蛋白细胞骨架在极化上皮片的形态发生中的作用被普遍认为是重要的，但在这个过程中肌动蛋白动力学的调节仍然不清楚。在这里，我们表明，尖端加帽蛋白Tmod 3有助于上皮细胞的形状内融合单层极化上皮细胞。Tmod 3定位于几种细胞类型的极化上皮中的侧细胞膜。通过shRNA降低Tmod 3水平导致侧细胞膜的Factin和原肌球蛋白的损失，以及上皮细胞高度的降低，而不影响紧密连接或粘附连接蛋白的定位，或细胞-细胞粘附的任何明显变化。相反，分布在侧膜上的α II-血影蛋白被破坏后，减少Tmod 3的水平，这表明Tmod 3功能的损失导致不稳定和拆卸的原肌球蛋白包被的肌动蛋白丝，然后由解体的血影蛋白为基础的膜骨架上的侧膜。这些数据表明，第一次尖端帽的极化上皮细胞的形态调控，通过稳定的F-肌动蛋白对侧膜的作用。我们建议，Tmod 3帽原肌球蛋白肌动蛋白丝提供了至关重要的联系，在spectrin膜骨架的极化上皮细胞，使膜骨架保持细胞的形状。
Although the role of the actin cytoskeleton in morphogenesis of polarized epithelial sheets is generally accepted as centrally important, the regulation of actin dynamics in this process remains unclear. Here, we show that the pointed-end capping protein Tmod3 contributes to epithelial cell shape within confluent monolayers of polarized epithelial cells. Tmod3 localizes to lateral cell membranes in polarized epithelia of several cell types. Reduction of Tmod3 levels by shRNA leads to a loss of Factin and tropomyosins from lateral cell membranes, and a decrease in epithelial cell height, without effects on localisation of tight junction or adherens junction proteins, or any apparent changes in cell-cell adhesion. Instead, distribution of alpha II-spectrin on lateral membranes is disrupted upon reduction of Tmod3 levels, suggesting that loss of Tmod3 function leads to destabilization and disassembly of tropomyosin-coated actin filaments followed by disorganization of the spectrin-based membrane skeleton on lateral membranes. These data demonstrate for the first time a role for pointed-end capping in morphology regulation of polarized epithelial cells through stabilization of F-actin on lateral membranes. We propose that Tmod3-capped tropomyosin-actin filaments provide crucial links in the spectrin membrane skeleton of polarized epithelial cells, enabling the membrane skeleton to maintain cell shape.