Elucidation of the mechanism of intracellular phosphatidylinositol trafficking by the Phs1 family

阐明 Phs1 家族细胞内磷脂酰肌醇运输的机制

• 批准号: 20687008
• 负责人: KIHARA Akio
• 金额: $ 16.31万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (A)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20687008/
• 关键词: 脂質; 代謝; 細胞内輸送; 脂肪酸; 極長鎖脂肪酸; スフィンゴ脂質; 遺伝子; タンパク質; ホスファチジルイノシトール; 脂質輸送; 生体膜; 縮合酵素; アシルCoA; 3-ヒドロキシアシルCoA脱水酵素

Phs1 is a 3-hydroxyacyl-CoA dehydratase involved in the elongation of very long-chain fatty acids (VLCFAs). We demonstrated here that Phs1 regulates sphingolipid synthesis and phosphatidylinositol transport through interacting with proteins involved in lipid metabolism and vesicular transport. We also succeeded in identifying mammalian homologs of Phs1, HACD1-4. By revealing substrate specificities of enzymes catalyzing the rate-limiting step of the VLCFA elongation, we have elucidated the entire VLCFA pathways in mammals. Moreover, we obtained some knowledge about relationship between VLCFA elongation and certain disorders.

Phs1是一种3-羟基酰辅酶A脱水酶，与超长链脂肪酸(VLCFAs)的延长有关。我们在这里证明了Phs1通过与脂代谢和囊泡运输相关的蛋白质相互作用来调节鞘磷脂的合成和磷脂酰肌醇的运输。我们还成功地鉴定了Phs1、HACD1-4的哺乳动物同源物。通过揭示催化VLCFA延长限速步骤的酶的底物特异性，我们已经阐明了哺乳动物VLCFA的整个通路。此外，我们还获得了一些关于VLCFA延长与某些疾病的关系的知识。

项目成果

Specificity of elongation of saturated, very long-chain fatty acids provides a link to C24 sphingolipid synthesis

饱和超长链脂肪酸伸长的特异性为 C24 鞘脂合成提供了联系

• 发表时间: 2010
• 作者: Kihara;A.
• 通讯作者: A.

Hetero-oligomeric interactions of an ELOVL4 mutant protein : implications in the molecular mechanism of Stargardt-3 macular dystrophy.

ELOVL4 突变蛋白的异寡聚相互作用：对 Stargardt-3 黄斑营养不良分子机制的影响。

• 发表时间: 2010
• 期刊: Mol.Vis. 16
• 作者: Okuda;A.;Naganuma;T.;Ohno;Y.;Abe;K.;Yamagata;M.;Igarashi;Y.;Kihara;A.
• 通讯作者: A.

極長鎖脂肪酸伸長酵素ELOVLの機能およびスフィンゴ脂質合成調節機構の解明

阐明极长链脂肪酸延长酶ELOVL的功能及鞘脂合成的调控机制

• 发表时间: 2010
• 作者: Nagakubo A;Sekine K;Tanaka Y;Kuranishi RB;Kanada S;Tojo K;大野祐介
• 通讯作者: 大野祐介

Membrane topology and essential amino acid residues of Phs1, a 3-hydroxyacyl-CoA dehydratase involved in very long-chain fatty acid elongation

• DOI: 10.1074/jbc.m708993200
• 发表时间: 2008-04-25
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Kihara, Akio;Sakuraba, Hiroko;Igarashi, Yasuyuki
• 通讯作者: Igarashi, Yasuyuki

Synthesis of very long-chain fatty acid and its relationship to sphingolipid metabolism

超长链脂肪酸的合成及其与鞘脂代谢的关系

• 发表时间: 2009
• 作者: Iwase A.;Mitsuda N.;Koyama K.;Hiratsu K;Kojima M.;Arai T.;Inoue Y.;Seki M.;Sakakibara H.;Sugimoto K.;Ohme-Takagi M.;坂口麻理・市栄智明・中川弥智子・酒井章子;Kihara A.
• 通讯作者: Kihara A.