Regulation of phospholipid dynamics in brain

Phospholipids are asymmetrically distributed at the plasma membrane. Phosphatidylserine (PtdSer) is exclusively located in the inner leaflet of the cell membrane while phosphatidylcholine (PtdCho) and glycolipids are mainly located in the outer leaflet of the membrane. However, this asymmetry is disrupted in various physiological situations, and PtdSer is exposed on the cell surface. In platelets, exposed PtdSer functions as a scaffold for the coagulation reaction, while in dead cells, exposed PtdSer serves as an Eat-me signal for efferocytosis. In the developing brain, synaptic connections are over-formed during the fetal period, but about half of the neurons are removed by apoptosis, and synaptic and dendritic compartments of living neurons are also removed by phagocytes. During these processes, glial cells such as microglia and astrocyte engulf unwanted dead cells and compartments in living cells using several phagocytic receptors, recognizing PtdSer by direct binding or an indirect way using secreted molecules. Based on recent findings, we will discuss how the compartments in living neurons are eliminated for the neuronal circuit plasticity. (c) 2021 Published by Elsevier B.V. 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 2. Removal of unwanted targets from tissues. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .31 2.1. Removal of unwanted cells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .31 2.2. Removal of unwanted compartments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 3. Regulation of PtdSer in brain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 3.1. PtdSer recognition by microglia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .33 3.2. Mechanism of PtdSer exposure in neuron . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 3.3. Role of the PtdSer flippase in brain development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34

Automated summary

Phospholipids are asymmetrically distributed in the plasma membrane, with phosphatidylserine (PtdSer) located exclusively in the inner leaflet and phosphatidylcholine (PtdCho) mainly in the outer leaflet. Disruption of this asymmetry can lead to exposure of PtdSer on the cell surface, serving different functions in processes such as coagulation and efferocytosis. In the brain, phagocytes recognize and remove unwanted dead cells and cell compartments via direct or indirect binding to PtdSer, contributing to neuronal circuit plasticity.