Spatio-temporal analysis of DOCK180 during dorsal ruffle formation

DOCK180在背皱形成过程中的时空分析

• 批准号: 24770127
• 负责人: SANEMATSU FUMIYUKI
• 金额: $ 3万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24770127/
• 关键词: ラッフル膜形成; Rac活性化分子; DOCK180; 細胞骨格; Rac; ホスファチジン酸; ラッフル膜

Activation of receptor tyrosine kinases leads to the formation of two different types of plasma membrane structures: peripheral ruffles and dorsal ruffles. Although the formation of both ruffle types requires activation of the small GTPase Rac, the difference in kinetics suggests that a distinct regulatory mechanism operates for their ruffle formation. DOCK1(DOCK180) and DOCK5 are atypical Rac activators and are both expressed in mouse embryonic fibroblasts (MEFs). We found that DOCK1 deficiency alone impaired dorsal ruffle formation in MEFs. DOCK1 bound to phosphatidic acid (PA) through the C-terminal polybasic amino acid cluster and was localized to dorsal ruffles. In addition, we show that phospholipase D, an enzyme that catalyzes PA synthesis, is required for PDGF-induced dorsal, but not peripheral, ruffle formation. These results indicate that the phospholipase D-PA axis selectively controls dorsal ruffle formation by regulating DOCK1 localization.

受体酪氨酸激酶的激活导致形成两种不同类型的质膜结构：外围荷叶边和背荷褶。尽管两种荷叶边类型的形成都需要激活小的GTPase RAC，但动力学的差异表明，一种独特的调节机制可用于其荷叶边的形成。 DOCK1（DOCK180）和DOCK5是非典型RAC激活剂，均以小鼠胚胎成纤维细胞（MEF）表示。我们发现，仅Dock1缺乏症就会损害MEF的背荷叶边形成。 DOCK1通过C末端的多边氨基酸簇与磷脂酸（PA）结合，并定位于背荷叶边。此外，我们表明磷脂酶D（一种催化PA合成的酶是PDGF诱导的背侧，但不是外围荷叶边形成所必需的。这些结果表明，磷脂酶D-PA轴通过调节DOCK1定位选择性控制背荷叶边的形成。

项目成果

Dorsal ruffle形成時におけるDOCK1の役割とその制御

DOCK1在背皱形成过程中的作用及其调节

• 发表时间: 2012
• 作者: 實松史幸;錦見昭彦;渡邉真裕紀;本宮綱記;田中芳彦;金保安則;Jean-Francois Cote;福井宣規
• 通讯作者: 福井宣規

Role of DOCK1 and its regulation during dorsal ruffle formation.

DOCK1 的作用及其在背皱形成过程中的调节。

• 发表时间: 2012
• 作者: Sanematsu F;Nishikimi A;Watanabe M;Hongu T;Tanaka Y;Kanaho Y;Jean-Francois Cote;Fukui Y
• 通讯作者: Fukui Y

心血管形成におけるDOCK180の機能とその制御機構

DOCK180在心血管形成中的作用及其调控机制

• 发表时间: 2012
• 期刊: 感染・炎症・免疫
• 作者: S.Kamio;Q.Cao;K.Abe;T.Yamada M.Inomoto;Y.Ono;等;Nishikimi A;鈴木勉;矢野直峰;實松史幸
• 通讯作者: 實松史幸

The Rac activator DOCK2 regulates natural killer cell-mediated cytotoxicity in mice through the lytic synapse formation

• DOI: 10.1182/blood-2012-12-475897
• 发表时间: 2013-07-18
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Sakai, Yusuke;Tanaka, Yoshihiko;Fukui, Yoshinori
• 通讯作者: Fukui, Yoshinori

Blockade of Inflammatory Responses by a Small-Molecule Inhibitor of the Rac Activator DOCK2

• DOI: 10.1016/j.chembiol.2012.03.008
• 发表时间: 2012-04-20
• 期刊: CHEMISTRY & BIOLOGY
• 作者: Nishikimi, Akihiko;Uruno, Takehito;Fukui, Yoshinori
• 通讯作者: Fukui, Yoshinori