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A lysophospholipid acyltransferase antagonist, CI-976, creates novel membrane tubules marked by intracellular phospholipase A1 KIAA0725p

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Abstract

CI-976 is a lysophospholipid acyltransferase antagonist that is known to affect secretory and endocytic membrane-trafficking pathways likely by increasing the lysophospholipid content in membranes. Our previous study suggested that lysophospholipids formed through the action of an intracellular phospholipase A1, KIAA0725p (also known as DDHD2 and iPLA1γ), may be important for the association of this enzyme with membranes. In this study, we examined the effect of CI-976 on the membrane association of KIAA0725p. While in HeLa cells KIAA0725p is localized in the Golgi and cytosol, in mouse embryonic fibroblasts (MEFs), it was found to be principally localized in the cytosol with some on post-endoplasmic reticulum compartments including the cis-Golgi. Treatment of MEFs with CI-976 induced the redistribution of KIAA0725p to membrane tubules, which were in vicinity to fragmented mitochondria. These tubules were not decorated with canonical organelle markers including Golgi proteins. A human KIAA0725p mutant, which exhibits decreased membrane-binding ability, was also redistributed to membrane structures upon CI-976 treatment. Our data suggest that the association of KIAA0725p with membranes is regulated by lipid metabolism, and that CI-976 may create unique membrane structures that can be marked by KIAA0725p.

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Acknowledgments

This work was supported in part by a Grants-in-Aid for Scientific Research, 20570190, to KT from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. We thank Ms. Y. Mizuya for her assistance.

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Authors and Affiliations

  1. School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, 192-0392, Japan

    Takashi Baba, Mitsuo Tagaya & Katsuko Tani

  2. Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga, 526-0829, Japan

    Akitsugu Yamamoto

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  1. Takashi Baba
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  2. Akitsugu Yamamoto
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  3. Mitsuo Tagaya
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  4. Katsuko Tani
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Correspondence to Katsuko Tani.

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Baba, T., Yamamoto, A., Tagaya, M. et al. A lysophospholipid acyltransferase antagonist, CI-976, creates novel membrane tubules marked by intracellular phospholipase A1 KIAA0725p. Mol Cell Biochem 376, 151–161 (2013). https://doi.org/10.1007/s11010-013-1563-4

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