Journal
JOURNAL OF CELL SCIENCE
Volume 122, Issue 12, Pages 1970-1978Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.044743
Keywords
Peripheral ER; Lamin; Nuclear shape; Nuclear architecture; Lipid droplets; Diabetes; Insulin resistance; Majeed syndrome
Categories
Funding
- Intramural NIH HHS Funding Source: Medline
- NIGMS NIH HHS [R01 GM066953] Funding Source: Medline
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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.
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