Inactivation of the C. elegans lipin homolog leads to ER disorganization and to defects in the breakdown and reassembly of the nuclear envelope.
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.
Golden
Andy
A
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.
Liu
Jun
J
Cohen-Fix
Orna
O
D000818:Animals; D030801:Animals, Genetically Modified; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D002467:Cell Nucleus / Q000648:ultrastructure; D048750:Cell Nucleus Division / Q000187:drug effects / Q000235:genetics; D020090:Chromosome Segregation / Q000187:drug effects / Q000235:genetics; D004625:Embryo, Nonmammalian; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D020868:Gene Silencing / Q000502:physiology; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D009685:Nuclear Envelope / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D034741:RNA, Small Interfering / Q000494:pharmacology; D017385:Sequence Homology
D029742:Caenorhabditis elegans Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering