House Morgan, Khadayat Karan, Trybala Thomas N, Nambiar Nikhil, Jones Elizabeth, Abel Steven M, Baccile Joshua, Joshi Amit S
Department of Biochemistry & Cellular and Molecular Biology, University of Tennessee, Knoxville, TN, USA.
Department of Chemistry, University of Tennessee, Knoxville, TN, USA.
J Cell Biol. 2025 Jul 7;224(7). doi: 10.1083/jcb.202405162. Epub 2025 May 23.
Lipid droplets (LDs) are ubiquitous neutral lipid storage organelles that form at discrete subdomains in the ER bilayer. The assembly of these ER subdomains and the mechanism by which proteins are recruited to them is poorly understood. Here, we investigate the spatiotemporal distribution of Pex30 at the ER-LD membrane contact sites (MCSs). Pex30, an ER membrane-shaping protein, has a reticulon homology domain, a dysferlin (DysF) domain, and a Duf4196 domain. Deletion of SEI1, which codes for seipin, a highly conserved protein required for LD biogenesis, results in accumulation of Pex30 and phosphatidic acid (PA) at ER-LD contact sites. We show that PA recruits Pex30 at ER subdomains by binding to the DysF domain. The distribution of Pex30 as well as PA is also affected by phosphatidylcholine (PC) levels. We propose that PA regulates the spatiotemporal distribution of Pex30 at ER subdomains that plays a critical role in driving the formation of LDs in the ER membrane.
脂滴（LDs）是普遍存在的中性脂质储存细胞器，在内质网（ER）双层膜的离散亚结构域形成。这些内质网亚结构域的组装以及蛋白质被招募到其上的机制尚不清楚。在这里，我们研究了Pex30在内质网-脂滴膜接触位点（MCSs）的时空分布。Pex30是一种内质网塑形蛋白，具有网状蛋白同源结构域、dysferlin（DysF）结构域和Duf4196结构域。编码seipin（脂滴生物发生所需的高度保守蛋白）的SEI1缺失，会导致Pex30和磷脂酸（PA）在内质网-脂滴接触位点积累。我们表明，PA通过与DysF结构域结合在内质网亚结构域招募Pex30。Pex30以及PA的分布也受磷脂酰胆碱（PC）水平的影响。我们提出，PA调节Pex30在内质网亚结构域的时空分布，这在内质网膜中驱动脂滴形成中起关键作用。
