期刊
MOLECULAR BIOLOGY OF THE CELL
卷 23, 期 24, 页码 4689-4700出版社
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E12-09-0673
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资金
- 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
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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