Intracellular phospholipase A1 and acyltransferase, which are involved in Caenorhabditis elegans stem cell divisions, determine the sn-1 fatty acyl chain of phosphatidylinositol.
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, -9, and -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 Caenorhabditis 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 A(1) 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.
Imae
Rieko
R
Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
Inoue
Takao
T
Kimura
Masako
M
Kanamori
Takahiro
T
Tomioka
Naoko H
NH
Kage-Nakadai
Eriko
E
Mitani
Shohei
S
Arai
Hiroyuki
H
D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D005227:Fatty Acids / Q000737:chemistry* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D009154:Mutation; D010716:Phosphatidylinositols / Q000737:chemistry* / Q000378:metabolism; D054466:Phospholipases A1 / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013229:Stearic Acids / Q000737:chemistry; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D005227:Fatty Acids; D010716:Phosphatidylinositols; D011993:Recombinant Fusion Proteins; D013229:Stearic Acids; C031183:stearic acid; D000217:Acyltransferases; D054466:Phospholipases A1