Getting to the Outer Leaflet: Physiology of Phosphatidylserine Exposure at the Plasma Membrane

Physiol Rev. 2016 Apr;96(2):605-45. doi: 10.1152/physrev.00020.2015.

Abstract

Phosphatidylserine (PS) is a major component of membrane bilayers whose change in distribution between inner and outer leaflets is an important physiological signal. Normally, members of the type IV P-type ATPases spend metabolic energy to create an asymmetric distribution of phospholipids between the two leaflets, with PS confined to the cytoplasmic membrane leaflet. On occasion, membrane enzymes, known as scramblases, are activated to facilitate transbilayer migration of lipids, including PS. Recently, two proteins required for such randomization have been identified: TMEM16F, a scramblase regulated by elevated intracellular Ca(2+), and XKR8, a caspase-sensitive protein required for PS exposure in apoptotic cells. Once exposed at the cell surface, PS regulates biochemical reactions involved in blood coagulation, and bone mineralization, and also regulates a variety of cell-cell interactions. Exposed on the surface of apoptotic cells, PS controls their recognition and engulfment by other cells. This process is exploited by parasites to invade their host, and in specialized form is used to maintain photoreceptors in the eye and modify synaptic connections in the brain. This review discusses what is known about the mechanism of PS exposure at the surface of the plasma membrane of cells, how actors in the extracellular milieu sense surface exposed PS, and how this recognition is translated to downstream consequences of PS exposure.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anoctamins
  • Apoptosis Regulatory Proteins / metabolism*
  • Cell Communication
  • Cell Membrane / metabolism*
  • Cytophagocytosis
  • Humans
  • Membrane Proteins / metabolism*
  • Phosphatidylserines / physiology*
  • Phospholipid Transfer Proteins / metabolism*

Substances

  • ANO6 protein, human
  • Anoctamins
  • Apoptosis Regulatory Proteins
  • Membrane Proteins
  • Phosphatidylserines
  • Phospholipid Transfer Proteins
  • Xkr8 protein, human