P4 ATPases - lipid flippases and their role in disease

Biochim Biophys Acta. 2009 Jul;1791(7):628-35. doi: 10.1016/j.bbalip.2009.02.008. Epub 2009 Feb 27.

Abstract

P4 ATPases (type 4 P-type ATPases) are multispan transmembrane proteins that have been implicated in phospholipid translocation from the exoplasmic to the cytoplasmic leaflet of biological membranes. Studies in Saccharomyces cerevisiae have indicated that P4 ATPases are important in vesicle biogenesis and are required for vesicular trafficking along several intracellular vesicular transport routes. Although little is known about mammalian P4 ATPases, some members of this subfamily appear to be associated with human disease or mouse pathophysiology. ATP8B1, a phosphatidylserine translocase, is the most extensively studied mammalian P4 ATPase. This protein is important for maintaining the detergent resistant properties of the apical membrane of the hepatocyte. Mutations in ATP8B1 give rise to severe liver disease. Furthermore, a role for Atp8b3 in mouse sperm cell capacitation has been suggested, whereas deficiency of Atp10a and Atp10d leads to insulin resistance and obesity in mice. Here we review the present status on the pathophysiological consequences of P4 ATPase deficiency.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / physiology*
  • Animals
  • Disease / genetics*
  • Humans
  • Lipids / physiology*
  • Membrane Transport Proteins / physiology
  • Mice
  • Mice, Knockout
  • Obesity / metabolism
  • Phospholipid Transfer Proteins / genetics
  • Phospholipid Transfer Proteins / physiology*

Substances

  • Lipids
  • Membrane Transport Proteins
  • Phospholipid Transfer Proteins
  • Adenosine Triphosphatases
  • ATP10a protein, mouse
  • ATP8B1 protein, human
  • Atp8b3 protein, mouse