Physiological significance of the fatty acid composition in phosphatidylinositol

磷脂酰肌醇脂肪酸组成的生理意义

• 批准号: 21770133
• 负责人: INOUE Takao
• 金额: $ 2.91万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21770133/
• 关键词: 細胞情報伝達機構; ホスファチジルイノシトール; アラキドン酸; 脂肪酸転移酵素

Phosphatidylinositol (PI), an important constituent of membranes, contains stearic acid as the major fatty acid at the sn-1 position. This fatty acid is thought to be incorporated into PI through fatty acid remodeling by sequential deacylation and reacylation. However, the genes responsible for the reaction are unknown, and consequently, the physiological significance of the sn-1 fatty acid remains to be elucidated. Here, we identified acl-8, acl-9, acl-10, which are closely related to each other, and ipla-1 as strong candidates for genes involved in fatty acid remodeling at the sn-1 position of PI. In both ipla-1 mutants and acl-8 acl-9 acl-10 triple mutants of C. elegans, the stearic acid content of PI is reduced and asymmetric division of stem cell-like epithelial cells is defective. The defects in asymmetric division of these mutants are suppressed by a mutation of the same genes involved in intracellular retrograde transport, suggesting that ipla-1 and acl genes act in the same pathway. IPLA-1 and ACL-10 have phospholipase A1 and acyltransferase activity, respectively, both of which recognize the sn-1 position of PI as their substrate. We propose that the sn-1 fatty acid of PI is determined by ipla-1 and acl-8, -9, -10 and crucial for asymmetric divisions.

磷脂酰肌醇（PI）是细胞膜的重要组成部分，其sn-1位置的主要脂肪酸为硬脂酸。这种脂肪酸被认为是通过连续去酰化和再酰化的脂肪酸重塑而被纳入PI的。然而，负责该反应的基因是未知的，因此，sn-1脂肪酸的生理意义仍有待阐明。在这里，我们确定了彼此密切相关的acl-8， acl-9， acl-10和ipla-1作为参与PI sn-1位置脂肪酸重塑的基因的强候选基因。在秀丽隐杆线虫的ipla-1突变体和acl-8 - acl-9 - acl-10三重突变体中，PI的硬脂酸含量降低，干细胞样上皮细胞的不对称分裂缺陷。这些突变体的不对称分裂缺陷被参与细胞内逆行运输的相同基因的突变所抑制，这表明ipla-1和acl基因在相同的途径中起作用。IPLA-1和ACL-10分别具有磷脂酶A1和酰基转移酶活性，两者都能识别PI的sn-1位置作为其底物。我们认为PI的sn-1脂肪酸是由ipla-1和acl-8， -9， -10决定的，对不对称分裂至关重要。

项目成果

線虫C.elegansを用いた生体膜脂質の機能解析

使用线虫进行生物膜脂质的功能分析

• 发表时间: 2010
• 作者: Kouzmenko;A ; Ohtake;F ; Fujiki;R;Kato S;井上貴雄
• 通讯作者: 井上貴雄

ホームページ等。

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mboa-7/LPIAT is required for selective incorporation of polyunsaturated fatty acids into phosphatidylinositol

mboa-7/LPIAT 是选择性地将多不饱和脂肪酸掺入磷脂酰肌醇所必需的

• 发表时间: 2009
• 作者: 中崎康子

Functions of PUFA-containing phospholipids in C.elegans

线虫中含 PUFA 的磷脂的功能

• 发表时间: 2010
• 作者: T.Shima;K.Sutoh;T.Kon;松田真治;松田真治;松田真治;松田真治
• 通讯作者: 松田真治

線虫C.elegansを用いた脂肪酸リモデリング酵素の包括的解析

使用秀丽隐杆线虫对脂肪酸重塑酶进行综合分析

• 发表时间: 2010
• 作者: Masatoshi Maki;Hironori Suzuki;Hideki Shibata;井上貴雄
• 通讯作者: 井上貴雄