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受调控的极化磷脂酰肌醇-3,4,5-三磷酸(PtdIns(3,4,5)P3)积累对于感光上皮细胞顶端膜形态发生至关重要。

Regulated and polarized PtdIns(3,4,5)P3 accumulation is essential for apical membrane morphogenesis in photoreceptor epithelial cells.

作者信息

Pinal Noelia, Goberdhan Deborah C I, Collinson Lucy, Fujita Yasuyuki, Cox Iain M, Wilson Clive, Pichaud Franck

机构信息

Medical Research Council Laboratory for Molecular Cell Biology and Cell Biology Unit, Department of Anatomy and Developmental Biology, University College London, Gower Street, WC1E 6BT London, United Kingdom.

出版信息

Curr Biol. 2006 Jan 24;16(2):140-9. doi: 10.1016/j.cub.2005.11.068.

Abstract

BACKGROUND

In a specialized epithelial cell such as the Drosophila photoreceptor, a conserved set of proteins is essential for the establishment of polarity, its maintenance, or both--in Drosophila, these proteins include the apical factors Bazooka, D-atypical protein kinase C, and D-Par6 together with D-Ecadherin. However, little is known about the mechanisms by which such apical factors might regulate the differentiation of the apical membrane into functional domains such as an apical-most stack of microvilli or more lateral sub-apical membrane.

RESULTS

We show that in photoreceptors Bazooka (D-Par3) recruits the tumor suppressor lipid phosphatase PTEN to developing cell-cell junctions (Zonula Adherens, za). za-localized PTEN controls the spatially restricted accumulation of optimum levels of the lipid PtdIns(3,4,5)P3 within the apical membrane domain. This in turn finely tunes activation of Akt1, a process essential for proper morphogenesis of the light-gathering organelle, consisting of a stack of F-actin rich microvilli within the apical membrane.

CONCLUSIONS

Spatially localized PtdIns(3,4,5)P3 mediates directional sensing during neutrophil and Dictyostelium chemotaxis. We conclude that a conserved mechanism also operates during photoreceptor epithelial cell morphogenesis in order to achieve normal differentiation of the apical membrane.

摘要

背景

在诸如果蝇光感受器这样的特化上皮细胞中,一组保守的蛋白质对于极性的建立、维持或两者兼而有之至关重要——在果蝇中,这些蛋白质包括顶端因子巴祖卡(Bazooka)、D-非典型蛋白激酶C、D-Par6以及D-钙黏蛋白。然而,对于这些顶端因子可能调控顶端膜分化为功能域(如最顶端的微绒毛堆叠或更靠外侧的顶端下膜)的机制知之甚少。

结果

我们发现,在光感受器中,巴祖卡(D-Par3)将肿瘤抑制脂质磷酸酶PTEN招募至正在发育的细胞间连接(黏着连接,za)。定位在za的PTEN控制着顶端膜域内脂质PtdIns(3,4,5)P3最佳水平的空间限制积累。这进而精细调节Akt1的激活,Akt1的激活对于光收集细胞器的正常形态发生至关重要,光收集细胞器由顶端膜内富含F-肌动蛋白的微绒毛堆叠组成。

结论

空间定位的PtdIns(3,4,5)P3在中性粒细胞和盘基网柄菌趋化过程中介导方向感知。我们得出结论,一种保守机制在光感受器上皮细胞形态发生过程中也发挥作用,以实现顶端膜的正常分化。

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