Regulation of phospholipid dynamics in brain

Abstract

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.

Keywords: Astrocyte; Engulfment; Microglia; Neuron; Phosphatidylserine; Phospholipid; Pruning; Scramblase.