Determinants of Endoplasmic Reticulum-to-Lipid Droplet Protein Targeting.

Determinants of Endoplasmic Reticulum-to-Lipid Droplet Protein Targeting. Dev Cell. 2020 Jul 27;: Authors: Olarte MJ, Kim S, Sharp ME, Swanson JMJ, Farese RV, Walther TC Abstract Lipid droplet (LD) formation from the endoplasmic reticulum (ER) is accompanied by the targeting and accumulation of specific hydrophobic, membrane-embedded proteins on LDs. The determinants of this process are unknown. Here, we study the hydrophobic membrane motifs of two Drosophila melanogaster proteins, GPAT4 and ALG14, that utilize this pathway, and we identify crucial sequence features that mediate LD accumulation. Molecular dynamics simulations and studies in cells reveal that LD targeting of these motifs requires deeply inserted tryptophans that have lower free energy in the LD oil phase and positively charged residues near predicted hairpin hinges that become less constrained in the LD environment. Analyzing hydrophobic motifs from similar LD-targeting proteins, it appears that the distribution of tryptophan and positively charged residues distinguishes them from non-LD-targeting membrane motifs. Our studies identify specific sequence features and principles of hydrophobic membrane motifs that mediate their accumulation on LDs. PMID: 32730754 [PubMed - as supplied by publisher]
Source: Developmental Cell - Category: Cytology Authors: Tags: Dev Cell Source Type: research