Autotaxin – Lysophosphatidic acid (LPA).

Autotaxin is a lysophospholipase D that occurs in plasma and serum and cleaves lysophosphatidylcholine, thereby forming lysophosphatidic acid (LPA). This enzyme occurs as a 125 kDa protein, attached to intracellular vesicles with a single transmembrane domain, and as a soluble extracellular enzyme generated from the former by proteolytic processing and secretion.

  • Autotaxin appears to be a major source of extracellular LPA.
  • In mice expressing only one allele of autotaxin, plasma levels of LPA are half as high as in control mice.
  • Mice with homozygous autotaxin deficiency died around embryonic day 10 with major vascular defects in yolk sac and embryo.
  • They also had allantois malformation, neural tube defects and asymmetric headfolds. These symptoms strongly resemble the phenotype of Gα13 knockout mice, suggesting that LPA-GPCR predominantly signal through Gα13 in early development.

 

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