Targeting Fat: Mechanisms of Protein Localization to Lipid Droplets

Abstract

How proteins specifically localize to the phospholipid monolayer surface of lipid droplets (LDs) is being unraveled. We review here the major known pathways of protein targeting to LDs and suggest a classification framework based on the localization origin for the protein. Class I proteins often have a membrane-embedded, hydrophobic ‘hairpin’ motif, and access LDs from the endoplasmic reticulum (ER) either during LD formation or after formation via ER-LD membrane bridges. Class II proteins access the LD surface from the cytosol and bind through amphipathic helices or other hydrophobic domains. Other proteins require lipid modifications or protein-protein interactions to bind to LDs. We summarize knowledge for targeting and removal of the different classes, and highlight areas needing investigation.

The why, when and how of lipid droplet diversity

“…Step 3 -protein association with nascent lipid droplets Many proteins localize to lipid droplets through the ER (for examples, see Kory et al, 2016;Thiel et al, 2013;Zehmer et al, 2009), and it is thus likely that nascent lipid droplets recruit cytosolic or ER proteins during their emergence (Fig. 5).…”

The size matters: regulation of lipid storage by lipid droplet dynamics

“…Most of these enzymes are localized on ER where TAG is generated and transported to LDs through unknown mechanism (Kory et al, 2016). Certain subset of enzymes (ACSL1, ACSL3, ACSL4, GPAT4, AG-PAT3, Lipin1 and DGAT2) are reported to be specifically localized to LDs and promote local TAG synthesis and LD growth (Brasaemle et al, 2004;Fujimoto et al, 2007;Khelef et al, 1998; Kuerschner et al, 2008;Liu et al, 2004;Pol et al, 2014;Poppelreuther et al, 2012;Stone et al, 2009;Valdearcos et al, 2011;Wang et al, 2011;Wilfling et al, 2013).…”

Unique Motifs and Length of Hairpin in Oleosin Target the Cytosolic Side of Endoplasmic Reticulum and Budding Lipid Droplet

“…Cytoplasmic lipid droplets (LDs) of neutral lipids are present in diverse cells of eukaryotes and prokaryotes, including plants, mammals, nematodes, fungi, algae, and bacteria (Huang, 1992;Brasaemle and Wolins, 2012;Chapman et al, 2012;Murphy, 2012;Ruggles et al, 2013;Koch et al, 2014;Pol et al, 2014;Hashemi and Goodman, 2015;Welte, 2015;D'Aquila et al, 2016;Kory et al, 2016). The neutral lipids are usually triacylglycerols (TAGs) in plants and in addition steryl esters in mammals and yeast.…”