Physiological significance of the fatty acid composition in phosphatidylinositol

磷脂酰肌醇（PI）是膜的重要组成部分，在sn-1位含有硬脂酸作为主要脂肪酸。这种脂肪酸被认为是通过脂肪酸重塑通过顺序脱酰和再酰化并入PI中。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acl-8，acl-9，acl-10，这是密切相关的，和ipla-1作为强有力的候选基因参与脂肪酸重塑在sn-1位置的PI。在C. ipla-1突变体和acl-8、acl-9、acl-10三突变体中，在线虫中，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转运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。

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.