Journal
MOLECULAR BIOLOGY OF THE CELL
Volume 23, Issue 24, Pages 4689-4700Publisher
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E12-09-0673
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- Core Research for Evolutional Science and Technology, Japan Science and Technology Agency
- Program for Promotion of Basic and Applied Researches for Innovations in Bio-oriented Industry
- Japanese Ministry of Education, Culture, Sports, Science, and Technology [20370045]
- Japanese Ministry of Health, Labor, and Welfare
- Japan Society for the Promotion of Science for Young Scientists
- Grants-in-Aid for Scientific Research [20370045, 23227004] Funding Source: KAKEN
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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.
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