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

研究成果: Article査読

89 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)4689-4700
ページ数12
ジャーナルMolecular biology of the cell
23
24
DOI
出版ステータスPublished - 2012 12月 15
外部発表はい

ASJC Scopus subject areas

  • 分子生物学
  • 細胞生物学

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