Phospholipases

Abstract

Phospholipases play central roles in regulating signalling during numerous cellular events including proliferation, G protein‐coupled receptor signalling and neuronal activation by catalysing the lysis of phosphorylated lipids. In turn, second messengers are released, which control downstream events. Four distinct families of phospholipases have been described and are named A, B, C and D and range in size from 13 to 250 kDa. These enzyme family members are categorised based on the stereospecifically numbered sites within phospholipids where they promote cleavage. Within the phospholipase families, there are isoforms, which have differential distribution patterns and functions within specific cell types. These enzymes are widely expressed, can be regulated by different substrates or by [Ca2+] and can be found in the cytoplasm, membrane and in a soluble form outside of cells. Within the cytoplasm, different family members can be found within distinct organelles, including the mitochondria. In this article, we discuss these enzymes, their expression patterns and identified functions for each family member.

Key Concepts

  • Four different families of phospholipases control levels of phospholipid substrates by cleaving different sites of phospholipids.
  • Phospholipases are ubiquitously expressed in nature.
  • Phospholipase families are either calcium‐dependent or calcium‐independent enzymes.
  • Enzymes are often found in membranes, but some phospholipases are secreted.
  • Phospholipases have important functions in membrane integrity, digestion and cell signalling.
  • Phospholipases are important in health and certain disease states.

Keywords: phospholipids; phospholipase; signal transduction; lipoproteins; phosphatidylinositol; 4,5 bisphosphate; phosphatidylethanolamine; phosphatidylglycerol; phosphatidylserine

Figure 1. Generalised phospholipid structure indicating the sites of action of the phospholipase families A, B, C and D.
Figure 2. Isoforms of PLC.
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Further Reading

Cai A , Zheng D , Qiu R , Mai W and Zhou Y (2013) Lipoprotein‐associated phospholipase A2 (Lp‐PLA(2)): a novel and promising biomarker for cardiovascular risks assessment. Disease Markers 34 (5): 323–331.

Guo M , Pei R , Yang Q , et al. (2015) Phosphatidylserine‐specific phospholipase A1 involved in hepatitis C virus assembly through NS2 complex formation. Journal of Virology 89 (4): 2367–2377.

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Verma N and Figueredo VM (2014) HDL cholesterol: all hope is not lost after the torcetrapib setback – emerging therapeutic strategies on the horizon. American Journal of Therapy 21 (3): 222–232.

Zhang Y and Frohman MA (2014) Cellular and physiological roles for phospholipase D1 in cancer. Journal of Biological Chemistry 289 (33): 22567–22574.

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Vines, Charlotte M, and Bill, Colin A(May 2015) Phospholipases. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001394.pub3]