LPIAT1 regulates arachidonic acid content in phosphatidylinositol and is required for cortical lamination in mice

Hyeon Cheol Lee, Takao Inoue, Junko Sasaki, Takuya Kubo, Shinji Matsuda, Yasuko Nakasaki, Mitsuharu Hattori, Fumiharu Tanaka, Osamu Udagawa, Nozomu Kono, Toshiki Itoh, Hideo Ogiso, Ryo Taguchi, Makoto Arita, Takehiko Sasaki, Hiroyuki Arai

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Abstract

Dietary arachidonic acid (AA) has roles in growth, neuronal development, and cognitive function in infants. AA is remarkably enriched in phosphatidylinositol (PI), an impor tant constituent of biological membranes in mammals; however, the physiological signifi cance 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 selec tively 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. Immunohis tochemical analysis reveals disordered cortical lamination and delayed neuronal migration in the cortex of E18.5 Lpiat1 -/- mice. LPIAT1 deficiency also causes disordered neuronal pro cesses 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.

Original languageEnglish
Pages (from-to)4689-4700
Number of pages12
JournalMolecular biology of the cell
Volume23
Issue number24
DOIs
Publication statusPublished - 2012 Dec 15

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Lee, H. C., Inoue, T., Sasaki, J., Kubo, T., Matsuda, S., Nakasaki, Y., Hattori, M., Tanaka, F., Udagawa, O., Kono, N., Itoh, T., Ogiso, H., Taguchi, R., Arita, M., Sasaki, T., & Arai, H. (2012). LPIAT1 regulates arachidonic acid content in phosphatidylinositol and is required for cortical lamination in mice. Molecular biology of the cell, 23(24), 4689-4700. https://doi.org/10.1091/mbc.E12-09-0673