Abstract
Lipid droplets (LDs) have increasingly been recognized as an essential organelle for eukaryotes. Although the biochemistry of lipid synthesis and degradation is well characterized, the regulation of LD dynamics, including its formation, maintenance, and secretion, is poorly understood. Here, we report that mice lacking Occludin (Ocln) show defective lipid metabolism. We show that LDs were larger than normal along its biogenesis and secretion pathway in Ocln null mammary cells. This defect in LD size control did not result from abnormal lipid synthesis or degradation; rather, it was because of secretion failure during the lactation stage. We found that OCLN was located on the LD membrane and was bound to essential regulators of lipid secretion, including BTN1a1 and XOR, in a C-terminus–dependent manner. Finally, OCLN was a phosphorylation target of Src kinase, whose loss causes lactation failure. Together, we demonstrate that Ocln is a downstream target of Src kinase and promotes LD secretion by binding to BTN1a1 and XOR.
Highlights
Lipid droplets (LDs) are microscale structures that are ubiquitous in almost all eukaryotic cells
The observation that LDs were larger than normal was most likely a secondary defect because of their inability to be efficiently secreted and, as a result, continued to grow inside luminal cells of the Ocln null epithelium. Consistent with this conclusion, we found that the levels of various lipid metabolic components, including free fatty acids (FFAs), diacylglycerol (DAG), triacylglycerol (TAG), and fatty acid ethyl esters (FAEEs) were indistinguishable between Ocln control and null mammary glands (Fig 4G, 4H, 4I and 4J), further confirming that TG biochemistry is relatively normal in the mutant glands
We report that mice lacking Ocln show defective lipid metabolism
Summary
Lipid droplets (LDs) are microscale structures that are ubiquitous in almost all eukaryotic cells. They are composed of an inner hydrophobic core of neutral storage fats, the triglycerides (TGs), or cholesterol esters, and an outer layer of protein-coated phospholipid monolayer membrane [1]. An important means that a cell regulates its energy storage is by controlling LD sizes, which can vary from less than tens of nanometers in diameter in most cells to hundreds of micrometers that can fill an entire adipocyte [2]. Initially considered as passive energy storage depots, LDs have gained increasing recognition as a new organelle essential for various fundamental cellular processes, including lipid trafficking, vesicular transport, and metabolism [1,3].
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