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First published online June 3, 2009
doi: 10.1242/10.1242/jcs.044743
Research Article |
1 The Laboratory of Biochemistry and Genetics and National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 8 Center Drive, Bethesda, MD 20892, USA
3 The Laboratory of Molecular and Cellular Biology, National Institutes of Health, 8 Center Drive, Bethesda, MD 20892, USA
2 Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA
* Author for correspondence (e-mail: ornacf{at}helix.nih.gov)
Accepted 9 March 2009
The nuclear envelope (NE) is a dynamic structure, undergoing periods of growth, breakdown and reassembly during the cell cycle. In yeast, altering lipid synthesis by inactivating the yeast homolog of lipin, a phosphatidic acid phosphohydrolase, leads to disorganization of the peripheral ER and abnormal nuclear shape. These results suggest that lipid metabolism contributes to NE dynamics; however, since yeast undergo closed mitosis, the relevance of these observations to higher eukaryotes is unclear. In mammals, lipin has been implicated in adipose tissue differentiation, insulin resistance, lipid storage and obesity, but the underlying cellular defects caused by altering lipin levels are not known. Here, we identify the Caenorhabditis elegans lipin homolog (LPIN-1) and examine its affect on NE dynamics. We find that downregulating LPIN-1 by RNAi results in the appearance of membrane sheets and other abnormal structures in the peripheral ER. Moreover, lpin-1 RNAi causes defects in NE breakdown, abnormal chromosome segregation and irregular nuclear morphology. These results uncover cellular processes affected by lipin in metazoa, and suggest that lipid synthesis has a role in NE dynamics.
Key words: Peripheral ER, Lamin, Nuclear shape, Nuclear architecture, Lipid droplets, Diabetes, Insulin resistance, Majeed syndrome
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M. Gorjanacz and I. W. Mattaj Lipin is required for efficient breakdown of the nuclear envelope in Caenorhabditis elegans J. Cell Sci., June 15, 2009; 122(12): 1963 - 1969. [Abstract] [Full Text] [PDF] |
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