The role of the extracellular matrix in focal localization of signal molecules

细胞外基质在信号分子焦点定位中的作用

• 批准号: 17082008
• 负责人: HIRASAWA Eri
• 金额: $ 41.86万
• 依托单位: Juntendo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17082008/
• 关键词: 細胞外マトリックス; シグナル分子; ヘパラン硫酸プロテオグリカン; 神経; 筋; シグナル; ラミニン; パールカン; 神経細胞; 筋細胞; 超分子複合体; 神経突起伸長; メカニカルストレス; GM1ガングリオシド; NGF受容体; 細胞内シグナル

The extracellular matrix (ECM) plays an important role in cell behavior and fate through the formation of supramolecular complexes and regulation of signal pathways. This research project aimed to analyze the molecular mechanism of the supramolecular complex formation and to define the initial step of cell signal pathways induced by ECM. We have used cell processes of neurite outgrowth and muscle contraction as a model system for the project. In collaboration with Dr. Frederic Mercier of University of Hawaii, we have identified the specialized structure fractone in the adult neurogenic zone that consists of basement membrane components such as laminins and perlecan. Our results revealed that the basement membrane structure provides not only physical support for tissues, but also acts as a signal regulator in the proliferation and differentiation of neural progenitor cells (Krevier et al 2007). We also found that extracellular environments play a role in regulating mechanosensitive channels of synovial cells, which are implicated in the maintenance of joint homeostasis (Sakamoto et al.2010). We reported that perlecan, which surrounds skeletal muscle, is critical for homeostasis of skeletal muscle, and is a regulator for maintaining muscle fiber types in response to mechanical stress (Xu et al 2010). Our study regarding the role of ECM in maintenance and proliferation of neural stem cells is being prepared for publication.

细胞外基质（extracellular matrix，ECM）通过形成超分子复合物和调节信号通路对细胞的行为和命运起着重要作用。本研究的目的是分析细胞外基质形成超分子复合物的分子机制，并确定细胞外基质诱导细胞信号通路的起始步骤。我们使用神经突生长和肌肉收缩的细胞过程作为该项目的模型系统。在与夏威夷大学的Frederic Mercier博士的合作中，我们已经确定了成人神经源性区中的特化结构碎片，其由基底膜成分如层粘连蛋白和串珠蛋白组成。我们的研究结果表明，基底膜结构不仅为组织提供物理支持，而且还在神经祖细胞的增殖和分化中充当信号调节剂（Krevier et al 2007）。我们还发现，细胞外环境在调节滑膜细胞的机械敏感性通道中发挥作用，这与维持关节稳态有关（Sakamoto et al.2010）。我们报道了骨骼肌周围的串珠素对骨骼肌的稳态至关重要，并且是维持肌纤维类型以响应机械应力的调节剂（Xu et al 2010）。我们关于ECM在神经干细胞的维持和增殖中的作用的研究正在准备发表。

项目成果

Targeting perlecan in human keratinocytes reveals novel roles for perlecan in epidermal formation

• DOI: 10.1074/jbc.m509500200
• 发表时间: 2006-02-24
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Sher, I;Zisman-Rozen, S;Ron, D
• 通讯作者: Ron, D

Fractones : speciahzed extracellular matrix structures governing the stem cell niches

Fractones：控制干细胞生态位的特殊细胞外基质结构

• 发表时间: 2009
• 作者: Douet;V;et al.
• 通讯作者: et al.

Binding of laminin-1 to GM1 ganglioside in lipid rafts is critical for neurite outgrowth.

脂筏中层粘连蛋白-1 与 GM1 神经节苷脂的结合对于神经突生长至关重要。

• 发表时间: 2009
• 期刊: J Cell Sei. 122
• 作者: Ichikawa N;Iwabuchi K;Kurihara H;Ishii K;Kobayashi T;Sasaki T;Hattori N;Mizuno Y;Hozumi K;Yamada Y;Arikawa-Hirasawa E*.
• 通讯作者: Arikawa-Hirasawa E*.

Targeting perlecan in human keratinocytes reveals novel roles for perlecan in epidermis formation.

靶向人类角质形成细胞中的基底膜聚糖揭示了基底膜聚糖在表皮形成中的新作用。

• 发表时间: 2006
• 期刊: J.Biol.Chem. 281(8)
• 作者: Sher;I.;Zisman-Rozen;S.;Eliahu L;Whitelock JM;Maas-Szabowski N;Yamada Y;Breitkreutz D;Fusenig NE;Arikawa-Hirasawa E;Iozzo RV;Bergman R;Ron D
• 通讯作者: Ron D

Testicular proteins associated with the germ cell-marker, TEX101 : Involvement of cellubrevin in TEX101-trafficking to the cell surface during spermatogenesis

与生殖细胞标记 TEX101 相关的睾丸蛋白：cellubrevin 参与精子发生过程中 TEX101 运输到细胞表面的过程

• 发表时间: 2006
• 期刊: Biochem Biophys Res Commun 345
• 作者: Hiroki Tsukamoto;Hiroshi Yoshitake;Miki Mori;Mitsuaki Yanagida;Kenji Takamori;Hideoki Ogawa;Toshihiro Takizawa;Yoshihiko Araki
• 通讯作者: Yoshihiko Araki