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Maintenance of the diacylglycerol level in the Golgi apparatus by the Nir2 protein is critical for Golgi secretory function

Nature Cell Biology volume 7, pages 225–234 (2005)Cite this article

A Corrigendum to this article was published on 01 April 2005

Abstract

The level of diacylglycerol (DAG) in the Golgi apparatus is crucial for protein transport to the plasma membrane. Studies in budding yeast indicate that Sec14p, a phosphatidylinositol (PI)-transfer protein, is involved in regulating DAG homeostasis in the Golgi complex. Here, we show that Nir2, a peripheral Golgi protein containing a PI-transfer domain, is essential for maintaining the structural and functional integrity of the Golgi apparatus in mammalian cells. Depletion of Nir2 by RNAi leads to substantial inhibition of protein transport from the trans-Golgi network to the plasma membrane, and causes a reduction in the DAG level in the Golgi apparatus. Remarkably, inactivation of the cytidine 5′-diphosphate (CDP)-choline pathway for phosphatidylcholine biosynthesis restores both effects. These results indicate that Nir2 is involved in maintaining a critical DAG pool in the Golgi apparatus by regulating its consumption via the CDP-choline pathway, demonstrating the interface between secretion from the Golgi and lipid homeostasis.

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Figure 1: Depletion of Nir2 by RNAi affects the Golgi architecture.
Figure 2: Depletion of Nir2 attenuates protein transport to the plasma membrane.
Figure 3: Inhibition of protein transport from the TGN to the plasma membrane in Nir2-depleted cells.
Figure 4: Depletion of Nir2 reduces the DAG level in the Golgi apparatus.
Figure 5: The PI-transfer domain is required for Nir2 function in the Golgi.
Figure 6: The ability to produce DAG from ceramide and PC is not affected by Nir2 depletion.
Figure 7: Nir2 regulates the consumption of DAG in the Golgi via the CDP-choline pathway for PC biosynthesis.

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Acknowledgements

We thank Z. Elazar, M. Liscovitch and A. Futerman for stimulating discussions. We also thank members of the Futerman laboratory (S. Boldin, Y. Kacher and M. Jmoudiak) for assistance in lipid analysis. Finally, we thank C. Brodie for the GFP–PKD construct. S. L. is an incumbent of the Helena Rubinstein Career Development Chair. This work was supported by the Israel Science Foundation (No. 1073/03), the Israel Cancer Research Foundation, and by the Harry and Jeanette Weinberg Fund for the Molecular Genetics of Cancer.

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  1. Vladimir Litvak and Nili Dahan: These two authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neurobiology, Weizmann Institute of Science, Rehovot, 76100, Israel

    Vladimir Litvak, Nili Dahan, Sreekumar Ramachandran & Sima Lev

  2. Electron Microscopy unit, Weizmann Institute of Science, Rehovot, 76100, Israel

    Helena Sabanay

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Correspondence to Sima Lev.

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Litvak, V., Dahan, N., Ramachandran, S. et al. Maintenance of the diacylglycerol level in the Golgi apparatus by the Nir2 protein is critical for Golgi secretory function. Nat Cell Biol 7, 225–234 (2005). https://doi.org/10.1038/ncb1221

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