Surface features of the lipid droplet mediate perilipin 2 localization
Open accessAbstract
All eukaryotic organisms store excess lipid in intracellular lipid droplets. These dynamic structures are associated with and regulated by numerous proteins. Perilipin 2, an abundant protein on most lipid droplets, promotes neutral lipid accumulation in lipid droplets. However, the mechanism by which perilipin 2 binds to and remains anchored on the lipid droplet surface is unknown. Here we identify features of the lipid droplet surface that influence perilipin 2 localization. We show that perilipin 2 binding to the lipid droplet surface requires both hydrophobic and electrostatic interactions. Reagents that disrupt these interactions also decrease binding. Moreover, perilipin 2 binding does not depend on other lipid droplet-associated proteins but is influenced by the lipid composition of the surface. Perilipin 2 binds to synthetic vesicles composed of dioleoylphosphatidylcholine, a phospholipid with unsaturated acyl chains. Decreasing the temperature of the binding reaction, or introducing phospholipids with saturated acyl chains, decreases binding. We therefore demonstrate a role for surface lipids and acyl chain packing in perilipin 2 binding to lipid droplets. The ability of the lipid droplet phospholipid composition to impact protein binding may link changes in nutrient availability to lipid droplet homeostasis.
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Lipid droplets with higher levels of unsaturation exhibit packing defects and increased protein binding.
“Several biophysical studies have reported that lipid droplets with higher levels of unsaturation exhibit packing defects and increased protein binding55,56.”
From APOE genotypes differentially remodel the astrocytic lipid droplet proteome to shape lipid droplet dynamics (2026) · cites this paper as [55]
Results §3.4 shows that unsaturated phospholipid vesicles were less tightly packed and bound more perilipin 2 than the comparison vesicles. The Discussion §4 also reports perilipin 2 on unsaturated, fluid lipid droplets, but says the role of packing in protein binding to droplet surfaces in vivo remains obscure. The source therefore does not establish packing defects and increased protein binding as a general property of more-unsaturated lipid droplets. (LLM, conf=0.86)
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Research works printed but not linked: 30
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Cited by
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Cuní-López, C., Root, J. T., Hao, Y., Blomberg, N., Koppes-den Hertog, S. J., Sacks, D., Trujillo, A. E., Ghirlando, R., Kowal, I., Epstein, J., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-76565-6
- Authors
- Sletten, A., Seline, A., Rudd, A., Logsdon, M., & Listenberger, L. L.
- Affiliations
- St. Olaf College (US)
- Corresponding author
- Listenberger, Laura L.
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2014-09
- Volume
- 452
- Issue
- 3
- Pages
- 422-427
- ISSN
- 0006-291X (ISSN-L)
- PMC
- PMC4184465
- OpenAlex
- W2074319127
- Cited by
- 34
- References
- 0
- Citations by year
- 2026: 3 · 2023: 3 · 2021: 2 · 2020: 5 · 2019: 3 · 2018: 6 · 2017: 1 · 2016: 5 · 2015: 5
- FWCI
- 1.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health Ruth L. Kirschstein National Research Service Award (1 F32 GM-074453-01)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- PLIN2, lipid droplets, hydrophobic interactions, electrostatic interactions, lipid composition, acyl chain packing, DOPC, synthetic vesicles, lipid droplet homeostasis, fat deposition
- MeSH terms
- Perilipin-2, Binding Sites, Humans, Liposomes, Membrane Proteins, Phosphatidylcholines, Protein Binding, Gene Expression, Static Electricity, HEK293 Cells, Hydrophobic and Hydrophilic Interactions, Proteolysis, Lipid Droplets
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