Fig. 2

Current knowledge of roles and intracellular transport of PtdSer. PtdSer is produced in the ER, from where it is distributed throughout the cell. PtdSer can be transferred to the mitochondria through mitochondria associated membranes (MAMs) (1), where it is mostly converted to PtdEtn. Distribution to the PM and endosomal system can occur via traditional vesicle-mediated trafficking as well as via direct movement via PtdSer-specific lipid transfer proteins (2). The relative importance of both trafficking methods is currently unclear. At the PM (3), PtdSer is kept in the cytoplasmic-facing leaflet and is important for generating a high net-negative charge. A number of important signaling molecules are recruited to the PM through charge and/or direct PtdSer recognition binding, with PtdSer thus playing essential roles in many signaling cascades and protein localization. PtdSer also plays important roles in endocytosis (4), including through its curvature-inducing headgroup interactions as well as interactions with proteins required for caveolae formation. PtdSer may also play a role in Golgi function (5), related to cargo sorting and budding from the trans-Golgi. PtdSer also appears to be important for recycling of cargo and interaction with the recycling machinery (e.g. Evectin2, EHD1, Snx4) at the recycling endosome (6). These interactions with the recycling machinery also likely helps to ensure PtdSer returns to, and maintains its enrichment on, the PM while causing reduced PtdSer levels on the late endosomes and lysosomes. Mito – mitochondria, ER – endoplasmic reticulum, PM – plasma membrane, EV – exocytic vesicle, EE – endocytic vesicle, RE – recycling endosome, Lys – lysosome