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Identification of small subunit of serine palmitoyltransferase a as a lysophosphatidylinositol acyltransferase 1‐interacting protein
Author(s) -
Hirata Yusuke,
Yamamori Natsumi,
Kono Nozomu,
Lee HyeonCheol,
Inoue Takao,
Arai Hiroyuki
Publication year - 2013
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12046
Subject(s) - biology , acyltransferase , carnitine o palmitoyltransferase , biochemistry , protein subunit , immunoprecipitation , microsome , mitochondrion , phosphatidylinositol , gene knockdown , inner mitochondrial membrane , phospholipid , serine , enzyme , microbiology and biotechnology , gene , signal transduction , membrane , beta oxidation
Lysophosphatidylinositol acyltransferase 1 ( LPIAT 1), also known as MBOAT 7, is a phospholipid acyltransferase that selectively incorporates arachidonic acid ( AA ) into the sn ‐2 position of phosphatidylinositol ( PI ). We previously demonstrated that LPIAT 1 regulates AA content in PI and plays a crucial role in brain development in mice. However, how LPIAT 1 is regulated and which proteins function cooperatively with LPIAT 1 are unknown. In this study, using a split‐ubiquitin membrane yeast two‐hybrid system, we identified the small subunit of serine palmitoyltransferase a (ss SPT a) as an LPIAT 1‐interacting protein. ss SPT a co‐immunoprecipitated and colocalized with LPIAT 1 in cultured mammalian cells. Knockdown of ss SPT a decreased the LPIAT 1‐dependent incorporation of exogenous AA into PI but did not affect the in vitro enzyme activity of LPIAT 1 in the microsomal fraction. Interestingly, knockdown of ss SPT a decreased the protein level of LPIAT 1 in the crude mitochondrial fraction but not in total homogenate or the microsomal fraction. LPIAT 1 was localized to the mitochondria‐associated membrane ( MAM ), where AA ‐selective acyl‐CoA synthetase is enriched. These results suggest that ss SPT a plays a role in fatty acid remodeling of PI , probably by facilitating the MAM localization of LPIAT 1.