Surface features of the lipid droplet mediate perilipin 2 localization

Abstract

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.

Protein Crowding Is a Determinant of Lipid Droplet Protein Composition

“…For example, the binding of some proteins, such as HSL, ATGL, CGI58, and CCT1, is regulated by protein phosphorylation depending on metabolic state (Egan et al, 1992; Arnold et al, 1997; Brasaemle et al, 2000; Sahu-Osen et al, 2014; Xie et al, 2014). In addition, during LD expansion, surface lipid composition of LDs, such as deficiency of PC, influences the binding of CCT, and possibly of other LD proteins, to LDs to facilitate growth (Arnold et al, 1997; Jamil and Vance, 1990; Krahmer et al, 2012; Sletten et al, 2014). These mechanisms likely represent other layers of regulation that work in concert with protein crowding to control LD protein composition.…”

Lysophosphatidylcholine acyltransferase 1 is downregulated by hepatitis C virus: impact on production of lipo-viro-particles

“…The interaction of these proteins with the LD surface can be modulated through mechanisms, probably of multiple causes, that are only just starting to be clarified 16 17. Because of the large variety of PLs conferring different physicochemical properties to the LD surface, the nature of PLs is a factor that can modulate the strength of protein association 18 19. The most abundant PL of the LD surface is phosphatidylcholine 20.…”

Insertion of perilipin 3 into a glycero(phospho)lipid monolayer depends on lipid headgroup and acyl chain species

“…free in the cytosol (44,45). The expression of perilipins 1 and 4 is confined to adipocytes and steroidogenic cells (18, 37-39, 41, 46), while perilipin 2 and perilipin 3 are ubiquitously expressed (19,42,43).…”