Seipin is required for converting nascent to mature lipid droplets

Abstract

How proteins control the biogenesis of cellular lipid droplets (LDs) is poorly understood. Using Drosophila and human cells, we show here that seipin, an ER protein implicated in LD biology, mediates a discrete step in LD formation—the conversion of small, nascent LDs to larger, mature LDs. Seipin forms discrete and dynamic foci in the ER that interact with nascent LDs to enable their growth. In the absence of seipin, numerous small, nascent LDs accumulate near the ER and most often fail to grow. Those that do grow prematurely acquire lipid synthesis enzymes and undergo expansion, eventually leading to the giant LDs characteristic of seipin deficiency. Our studies identify a discrete step of LD formation, namely the conversion of nascent LDs to mature LDs, and define a molecular role for seipin in this process, most likely by acting at ER-LD contact sites to enable lipid transfer to nascent LDs.DOI: http://dx.doi.org/10.7554/eLife.16582.001

Establishing the lipid droplet proteome: Mechanisms of lipid droplet protein targeting and degradation

“…At the junction of other organelles connected by contiguous membranes there are often proteins that regulate the diffusion barriers to maintain the correct proteomes, such as septin 2 at the junction between the plasma membrane and primary cilium [102] and the nuclear pore complex at the junction between the inner and outer nuclear membranes [103]. Seipin is positioned at ER-LD contact sites [41,42,44,104], but whether seipin or another protein acts as a “gatekeeper” to control protein diffusion between the ER and LDs is unknown.…”

“…HPos) and GPAT4 (i.e. livedrop), become concentrated at LD biogenesis sites in the ER [41,53]. Finally, differences in protein stability may also contribute to the asymmetric distribution of proteins between organelles (Fig.…”

The collaborative work of droplet assembly

“…Delay in droplet assembly in the absence of seipin has also been seen in Drosophila S2 cells [46]. A probe, termed LiveDrop, consisting of the droplet-associating domain of GPAT4 linked to Cherry, was developed.…”

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

“…In addition to the above mentioned LD growth and degradation pathways, the sizes of LDs and the intracellular lipid storage capacity are regulated by several other factors including Seipin, Pnpla3, Hsd17b13, Cavin and Ces1 (Bi et al, 2014;Cai et al, 2015;Cartwright et al, 2015;Grippa et al, 2015;Han et al, 2015;Romeo et al, 2008;Su et al, 2014;Szymanski et al, 2007;Wang et al, 2016;Wolinski et al, 2015). Seipin is originally discovered due to its mutation in severe congenital generalized lipodystrophy (Magré et al, 2001).…”