title: LPIAT1 regulates arachidonic acid content in phosphatidylinositol and is required for cortical lamination in mice.
abstract: Dietary arachidonic acid (AA) has roles in growth, neuronal development, and cognitive function in infants. AA is remarkably enriched in phosphatidylinositol (PI), an important constituent of biological membranes in mammals; however, the physiological significance of AA-containing PI remains unknown. In an RNA interference-based genetic screen using Caenorhabditis elegans, we recently cloned mboa-7 as an acyltransferase that selectively incorporates AA into PI. Here we show that lysophosphatidylinositol acyltransferase 1 (LPIAT1, also known as MBOAT7), the closest mammalian homologue, plays a crucial role in brain development in mice. Lpiat1(-/-) mice show almost no LPIAT activity with arachidonoyl-CoA as an acyl donor and show reduced AA contents in PI and PI phosphates. Lpiat1(-/-) mice die within a month and show atrophy of the cerebral cortex and hippocampus. Immunohistochemical analysis reveals disordered cortical lamination and delayed neuronal migration in the cortex of E18.5 Lpiat1(-/-) mice. LPIAT1 deficiency also causes disordered neuronal processes in the cortex and reduced neurite outgrowth in vitro. Taken together, these results demonstrate that AA-containing PI/PI phosphates play an important role in normal cortical lamination during brain development in mice.
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Hyeon-Cheol
authors.initials: HC
authors.lastname: Lee
authors.forename: Takao
authors.initials: T
authors.lastname: Inoue
authors.forename: Junko
authors.initials: J
authors.lastname: Sasaki
authors.forename: Takuya
authors.initials: T
authors.lastname: Kubo
authors.forename: Shinji
authors.initials: S
authors.lastname: Matsuda
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Nakasaki
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Hattori
authors.forename: Fumiharu
authors.initials: F
authors.lastname: Tanaka
authors.forename: Osamu
authors.initials: O
authors.lastname: Udagawa
authors.forename: Nozomu
authors.initials: N
authors.lastname: Kono
authors.forename: Toshiki
authors.initials: T
authors.lastname: Itoh
authors.forename: Hideo
authors.initials: H
authors.lastname: Ogiso
authors.forename: Ryo
authors.initials: R
authors.lastname: Taguchi
authors.forename: Makoto
authors.initials: M
authors.lastname: Arita
authors.forename: Takehiko
authors.initials: T
authors.lastname: Sasaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D016718:Arachidonic Acid / Q000378:metabolism*; D001284:Atrophy; D015153:Blotting, Western; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D057809:HEK293 Cells; D006624:Hippocampus / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016501:Neurites / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010716:Phosphatidylinositols / Q000378:metabolism*
chemical_list: D000217:Acyltransferases; D016718:Arachidonic Acid; D005227:Fatty Acids; D010716:Phosphatidylinositols; C581357:Mboat7 protein, mouse; C021522:lysophosphatidylinositol acyltransferase