Identification and molecular biological analysis of proteins involved in cell polarity

参与细胞极性的蛋白质的鉴定和分子生物学分析

• 批准号: 17390049
• 负责人: HARADA Akihiro
• 金额: $ 9.28万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390049/
• 关键词: cell polarity; epithelial cell; neuron; vesicular transport; membrane fusion; apical; basolateral; 遺伝学; 遺伝子; 細胞・組織; 蛋白質; バイオテクノロジー

We investigate under these two themes to gain insights into the mechanism of the vectorial transport1)Mechanism of cell polarization:Polarization of the cell is crucial to the proper function of various kinds of cells. Epithelial cells become polarized to have apical and basolateral sides to secrete enzymes or hormones efficiently. Neurons are also polarized to have dendrites and axons which is essential for neurotransmission. To investigate the mechanism of cell polarization, we are making knockout mice of proteins (rab8a, b, syntaxin3, VAMP7, SNAP23, FAPP1,2, PKD1,2, MAL2, Annexin13) crucial for this process. We have completed production of these knockout mice and are currently undertaking analyses of them by various cell biological and neurobiological methods. In addition, we are currently searching for novel proteins involved in cell polarity using cell culture systems as well as C.elegans as described below.2)Molecular mechanisms of vesicular transport in C.elegansEndocytosis is the vesicle-mediated cellular process required for many aspects of eukaryotic life, including nutrient uptake, membrane lipid and membrane protein recycling, antigen uptake by the immune system, synaptic vesicle recycling by the nervous system, and growth factor receptor regulation during development. In order to study endocytosis in multicellular organisms, we utilize advanced genetics available in a simple organism, C.elegans. C.elegans has the body that consists of cuticle, hypodermis, neurons, muscles, the intestine and gonad like the other animals. To identify novel components required for endocytosis, we are studying endocytosis-defective mutants of C.elegans. We are also interested in mechanisms of cell polarization and polarized protein transport in epithelial cells. We are planning to screen for mutants that have a defect in these mechanisms in C.elegans.

我们在这两个主题下进行了研究，以了解媒介传输的机理1）细胞极化机理：细胞的极化对于各种细胞的正确功能至关重要。上皮细胞变得两极分化，具有顶端和基底外侧的侧面，可以有效分泌酶或激素。神经元还具有极化，具有对神经传递至关重要的树突和轴突。为了研究细胞极化的机制，我们正在使蛋白质的基因敲除小鼠（Rab8a，b，syntaxin3，vamp7，snap23，snap23，fapp1,2，pkd1,2，pkd1,2，mal2，Annexin13）对于此过程至关重要。我们已经完成了这些敲除小鼠的生产，目前正在通过各种细胞生物学和神经生物学方法对它们进行分析。此外，我们目前正在使用细胞培养系统以及如下所述的C.级别搜索参与细胞极性的新型蛋白质。2）囊泡杂粒细胞增多症中囊泡转运的分子机制是囊泡介导的细胞介导的细胞介导的细胞过程，包括真实性化的许多方面，包括营养的膜，膜型和膜型植物倾向于养成植物的植物，并呈现膜的植物，并呈现膜，并呈现膜的植物，并呈现膜的植物，并呈现出膜的植物，并呈现出膜的凝聚力，并呈现出膜的凝聚力，并呈现出膜的植物凝聚力，并呈现出膜的凝聚力，并需要。神经系统的突触囊泡回收，以及发育过程中生长因子受体调节。为了研究多细胞生物的内吞作用，我们利用了简单生物体中可用的晚期遗传学。 C.Elegans具有由角质层，皮下注射，神经元，肌肉，肠和性腺的身体组成，就像其他动物一样。为了鉴定内吞作用所需的新成分，我们正在研究C.Elegans的内吞作用缺陷突变体。我们还对上皮细胞中细胞极化和极化蛋白转运的机制感兴趣。我们正计划筛选在C.Elegans中这些机制缺陷的突变体。

项目成果

Reduced expression of kinase-associated phosphatase in cortical dendrites of MAP2-deficient mice

• DOI: 10.1016/j.bbrc.2005.10.077
• 发表时间: 2005-12-16
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Iriuchijima, N;Sato-Harada, R;Harada, A
• 通讯作者: Harada, A

Pathogenesis and treatment of autosomal-dominant nephrogenic diabetes insipidus caused by an aquaporin 2 mutation

• DOI: 10.1073/pnas.0602331103
• 发表时间: 2006-09-19
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Sohara, Eisei;Rai, Tatemitsu;Uchida, Shinichi
• 通讯作者: Uchida, Shinichi

Dynamic regulation of caveolin-1 trafficking in the germ line and embryo of Caenorhabditis elegans

• DOI: 10.1091/mbc.e06-03-0211
• 发表时间: 2006-07-01
• 期刊: MOLECULAR BIOLOGY OF THE CELL
• 影响因子: 3.3
• 作者: Sato, Ken;Sato, Miyuki;Grant, Barth D.
• 通讯作者: Grant, Barth D.