The Step-Wise C-Truncation and Transport of ESyt3 to Lipid Droplets Reveals a Mother Primordial Cisterna

Abstract

AbstractExtended synaptotagmins (E-Syts) are endoplasmic reticulum (ER) proteins consisting of an SMP domain and multiple C2 domains that bind phospholipids and Ca2+. E-Syts create contact junctions between the ER and plasma membrane to facilitate lipid exchange. During adipocyte differentiation, the proteasome-based removal of the C2C domain results in targeting of E-Syt3 to the primordial cisterna, a previously undescribed giant annular organelle that mothers the LDs. Further cleavage causes the E-Syt3 relocation to the surface of LDs. Fragmentation of the primordial cisterna and LD budding into its lumen are early events in the biogenesis of LDs in the 3T3-L1 adipocyte. Electron tomography-based 3D reconstruction of the fragmented primordial cisterna revealed patches of a tightly packed E-Syt3-rich network of varicose tubules in close contact with young LDs. Esyt3 binds avidly phosphatidylethanolamine through its SMP domain, a main component of the LD membrane that fosters LD biogenesis. Repression of E-Syt3 effectively inhibits LD biogenesis and growth.