Spatio-temporal regulation of cellular trafficking and signal transduction

细胞运输和信号转导的时空调节

• 批准号: 21247031
• 负责人: MATSUMOTO Kunihiro
• 金额: $ 28.95万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21247031/
• 关键词: シグナル伝達; 細胞内トラフィック; プロテインキナーゼ; モーター蛋白質; LRRK1; EGFR; endosome; endocytosis; EGF受容; エンドサイトーシス; ダイニンモータ; ESCRT-0; MVB sortin; EGF受容体; MVB sorting

(1) Neurons are polarized cells that contain distinct sets of proteins in their axons and dendrites. Synaptic vesicles(SV) and many SV proteins are exclusively localized in the presynaptic regions but not in dendrites. We found that a MAPKKK-like kinase LRK-1 acts in the same pathway as UNC-16 and is required for the formation of proper volume of transport vesicles from Golgi apparatus.(2) Activation of the epidermal growth factor receptor(EGFR) triggers trafficking events that relocalize receptors from the cell surface to intracellular endocytic compartments. These events are important for the regulation of mitogenic EGFR signaling. We revealed that leucine-rich repeat kinase 1(LRRK1), a member of ROCO kinase family, forms a complex with activated EGFR through an interaction with Grb2 and is involved in the trafficking of EGFR from early to late endosomes. We showed that EGFR negatively regulates the kinase activity of LRRK1 by Tyr-944 phosphorylation and that this is required for proper endosomal trafficking of EGFR.

（1）神经元是极化细胞，其轴突和树突中包含不同的蛋白质集。突触囊泡（SV）和许多SV蛋白仅位于突触前区域，而不是在树突中。我们发现，类似MAPKKK的激酶LRK-1在与UNC-16相同的途径中起作用，是从高尔基体形成适当的运输囊泡所必需的。（2）激活表皮生长因子受体（EGFR）触发器的激活将受体从细胞表面重新定位到细胞内内吞室的运输事件。这些事件对于调节有丝分裂EGFR信号很重要。我们透露，洛科激酶家族的成员富含亮氨酸的重复激酶1（LRRK1），通过与GRB2的相互作用形成具有活化EGFR的复合物，并参与了EGFR从早期到后期内体的运输。我们表明，EGFR对Tyr-944磷酸化对LRRK1的激酶活性负面调节，这对于适当的EGFR内体贩运是必需的。

项目成果

線虫をモデル動物とした神経再生を誘導する因子/受容体の解析

以秀丽隐杆线虫为模型动物诱导神经再生的因子/受体分析

• 发表时间: 2010
• 作者: 李春;水野智亮;久本直毅;松本邦弘
• 通讯作者: 松本邦弘

Nemo-like kinase is involved in NGF-induced neurite outgrowth via phosphorylating MAP1B and paxillin

• DOI: 10.1111/j.1471-4159.2009.06400.x
• 发表时间: 2009-12-01
• 期刊: JOURNAL OF NEUROCHEMISTRY
• 影响因子: 4.7
• 作者: Ishitani, Tohru;Ishitani, Shizuka;Itoh, Motoyuki
• 通讯作者: Itoh, Motoyuki

Mib-Jag1-Notch signalling regulates patterning and structural roles of the notochord by controlling cell-fate decisions

• DOI: 10.1242/dev.051011
• 发表时间: 2010-08
• 期刊: Development
• 影响因子: 4.6
• 作者: Mai Yamamoto;Ryoko Morita;Takamasa Mizoguchi;Hiromi Matsuo;Miho Isoda;Tohru Ishitani;A. Chitnis;Kunihiro Matsumoto;J. G. Crump;K. Hozumi;S. Yonemura;K. Kawakami;Motoyuki Itoh

ROCOファミリーキナーゼLRRK1によるEGFR細胞内トラフィック制御

ROCO 家族激酶 LRRK1 对 EGFR 细胞内交通的调节

• 发表时间: 2009
• 作者: 花房洋;松本邦弘
• 通讯作者: 松本邦弘

Leucine-rich repeat kinase LRRK1 regulates endosomal trafficking of the EGF receptor.

• DOI: 10.1038/ncomms1161
• 发表时间: 2011-01-18
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Hanafusa, Hiroshi;Ishikawa, Kouki;Kedashiro, Shin;Saigo, Tsukasa;Iemura, Shun-ichiro;Natsume, Tohru;Komada, Masayuki;Shibuya, Hiroshi;Nara, Atsuki;Matsumoto, Kunihiro
• 通讯作者: Matsumoto, Kunihiro