Intracellular Lipid Droplets Contain Dynamic Pools of Sphingomyelin: ADRP Binds Phospholipids with High Affinity |
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Authors: | Avery L McIntosh Stephen M Storey Barbara P Atshaves |
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Affiliation: | (1) Department of Physiology and Pharmacology, Texas A&M University, TVMC, College Station, TX 77843, USA;(2) Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA; |
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Abstract: | During the last several years, intracellular lipid droplets have become the focus of intense study. No longer an inert bystander,
the lipid droplet is now known as a dynamic organelle contributing lipids to many cellular events. However, while the dynamics
of cholesterol efflux from both the plasma membrane and lipid droplets have been studied, less is known regarding the efflux
of sphingomyelin from these membranes. In order to address this issue, sphingomyelin efflux kinetics and binding affinities
from different intracellular pools were examined. When compared to the plasma membrane, lipid droplets had a smaller exchangeable
sphingomyelin efflux pool and the time required to efflux that pool was significantly shorter. Fluorescence binding assays
revealed that proteins in the plasma membrane and lipid droplet pool bound sphingomyelin with high affinity. Further characterization
identified adipose differentiation-related protein (ADRP) as one of the sphingomyelin binding proteins in the lipid droplet
fraction and revealed that ADRP demonstrated saturable binding to 6-((N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-hexanoyl)sphingosyl-phosphocholine (NBD-sphingomyelin) and also 2-(6-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)hexanoyl-1-hexadecanoyl-sn-glycero-3-phosphocholine (NBD-phosphatidylcholine) with binding affinities in the nanomolar range. Taken together, these
results suggest that lipid droplet associated proteins such as ADRP may play a significant role in regulating the intracellular
distribution of phospholipids and lipids in general. Overall, insights from the present work suggest new and important roles
for lipid droplets and ADRP in phospholipid metabolism. |
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