Neuronal plasma membrane phosphatidylserine domains (PS domains)

Neuronal plasma membrane phosphatidylserine (PS) domains are specialized lipid regions characterized by the presence or externalization of the anionic phospholipid phosphatidylserine. In healthy neurons, PS is primarily sequestered in the inner leaflet of the plasma membrane by the action of ATP-dependent flippases, maintaining membrane asymmetry (Segawa & Nagata, 2015, PubMed: 26433127). However, during apoptosis or sub-lethal cellular stress, PS is translocated to the outer leaflet by scramblases, where it acts as a potent 'eat-me' signal for microglia and other phagocytes (Scott-Hewitt et al., 2020, PubMed: 32493754). This process is essential for the clearance of apoptotic debris but can become pathological in neurodegenerative diseases like Alzheimer's and Parkinson's, where it triggers the premature removal of viable synapses, a process known as phagoptosis (Brown & Neher, 2014, PubMed: 24845144). Therapeutic targeting of these domains involves PS-binding molecules, such as Annexin V derivatives or monoclonal antibodies like bavituximab, which can be used for diagnostic imaging or to modulate the immune response (Gerber et al., 2015, PubMed: 25659451). Additionally, PS-targeting nanovesicles like SapC-DOPS are being explored for the selective delivery of drugs to stressed or malignant cells (Qi et al., 2009, PubMed: 19276382). By masking externalized PS, researchers aim to prevent aberrant synaptic pruning and preserve neuronal connectivity in chronic neurodegenerative conditions (UniProt, 2024; PubChem, 2024).

Other names

PhosphatidylserineExternalized phosphatidylserinePS-rich membrane domainsAminophospholipid domainsOuter leaflet phosphatidylserine

Binding to externalized phosphatidylserine to mask 'eat-me' signals, inhibit microglial phagocytosis of viable neurons, or deliver therapeutic cargo to stressed cells.