The luminal domain region of Seipin/Fld1 is dispensable for establishing functional ER sites for lipid droplet biogenesis.

ABSTRACT: Lipid droplet (LD) biogenesis occurs in the endoplasmic reticulum (ER), the mechanisms of which is not completely known. Seipin (Fld1 in yeast) is a crucial ER membrane protein that defines LD biogenesis sites. Here, we show that truncated seipin, Fld1-∆LR in yeast, and the human equivalent hSeipin-∆LR, mutants lacking the conserved luminal domain region (LR), functionally complement the LD biogenesis defect of fld1∆ mutants. Fld1-∆LR foci colocalize with factors: Nem1, Ldb16, Pex30 and Yft2, which are important for LD biogenesis and these sites become enriched in diacylglycerol upon stimulation of LD formation. Fld1-∆LR forms a homo-oligomeric complex facilitated by protein-protein interactions. We show that mutating the 31^st proline abrogates the functioning of Fld1-∆LR. We de

SUBMITTER: Khatri A 

PROVIDER: S-EPMC12660851 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature