Nuclear Phospholipase C Isoenzyme Imbalance Leads to Pathologies in Brain, Hematologic, Neuromuscular, and Fertility Disorders

J Lipid Res. 2019 Feb;60(2):312-317. doi: 10.1194/jlr.R089763. Epub 2018 Oct 4.

Abstract

Phosphoinositide-specific phospholipases C (PI-PLCs) are involved in signaling pathways related to critical cellular functions, such as cell cycle regulation, cell differentiation, and gene expression. Nuclear PI-PLCs have been studied as key enzymes, molecular targets, and clinical prognostic/diagnostic factors in many physiopathologic processes. Here, we summarize the main studies about nuclear PI-PLCs, specifically, the imbalance of isozymes such as PI-PLCβ1 and PI-PLCζ, in cerebral, hematologic, neuromuscular, and fertility disorders. PI-PLCβ1 and PI-PLCɣ1 affect epilepsy, depression, and bipolar disorder. In the brain, PI-PLCβ1 is involved in endocannabinoid neuronal excitability and is a potentially novel signature gene for subtypes of high-grade glioma. An altered quality or quantity of PI-PLCζ contributes to sperm defects that result in infertility, and PI-PLCβ1 aberrant inositide signaling contributes to both hematologic and degenerative muscle diseases. Understanding the mechanisms behind PI-PLC involvement in human pathologies may help identify new strategies for personalized therapies of these conditions.

Keywords: brain; fertility; myelodysplastic syndromes; myotonic dystrophy; nucleus; phospholipase C.

Publication types

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

MeSH terms

  • Animals
  • Brain Diseases / enzymology*
  • Brain Diseases / pathology
  • Cell Nucleus / enzymology*
  • Hematologic Diseases / enzymology*
  • Hematologic Diseases / pathology
  • Humans
  • Infertility / enzymology*
  • Infertility / pathology
  • Isoenzymes / metabolism
  • Neuromuscular Diseases / enzymology*
  • Neuromuscular Diseases / pathology
  • Type C Phospholipases / metabolism*

Substances

  • Isoenzymes
  • Type C Phospholipases