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PMID: 16782887 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Autotaxin, a secreted lysophospholipase D, is essential for blood vessel formation during development.

Molecular and cellular biology ·Vol. 26 ·No. 13 ·2006-07-00 ·Pages 5015-22

van Meeteren LA, Ruurs P, Stortelers C, Bouwman P, van Rooijen MA, Pradère JP, Pettit TR, Wakelam MJ, Saulnier-Blache JS, Mummery CL, Moolenaar WH, Jonkers J

Abstract

Autotaxin (ATX), or nucleotide pyrophosphatase-phosphodiesterase 2, is a secreted lysophospholipase D that promotes cell migration, metastasis, and angiogenesis. ATX generates lysophosphatidic acid (LPA), a lipid mitogen and motility factor that acts on several G protein-coupled receptors. Here we report that ATX-deficient mice die at embryonic day 9.5 (E9.5) with profound vascular defects in yolk sac and embryo resembling the Galpha13 knockout phenotype. Furthermore, at E8.5, ATX-deficient embryos showed allantois malformation, neural tube defects, and asymmetric headfolds. The onset of these abnormalities coincided with increased expression of ATX and LPA receptors in normal embryos. ATX heterozygous mice appear healthy but show half-normal ATX activity and plasma LPA levels. Our results reveal a critical role for ATX in vascular development, indicate that ATX is the major LPA-producing enzyme in vivo, and suggest that the vascular defects in ATX-deficient embryos may be explained by loss of LPA signaling through Galpha13.

MeSH Terms
Animals Blood Vessels/abnormalities,enzymology Embryo, Mammalian/abnormalities,blood supply,enzymology GTP-Binding Protein alpha Subunits, G12-G13/metabolism Genes, Lethal Lysophospholipids/blood,metabolism Mice Mice, Knockout Multienzyme Complexes/genetics,metabolism Phosphodiesterase I/genetics,metabolism Phosphoric Diester Hydrolases/genetics,metabolism Pyrophosphatases/genetics,metabolism Receptors, Lysophosphatidic Acid/genetics,metabolism
Chemicals
Lysophospholipids Multienzyme Complexes Receptors, Lysophosphatidic Acid Phosphoric Diester Hydrolases Phosphodiesterase I alkylglycerophosphoethanolamine phosphodiesterase Pyrophosphatases GTP-Binding Protein alpha Subunits, G12-G13 lysophosphatidic acid
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
van Meeteren Laurens A
Division of Cellular Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Ruurs Paula
Stortelers Catelijne
Bouwman Peter
van Rooijen Marga A
Pradère Jean Philippe
Pettit Trevor R
Wakelam Michael J O
Saulnier-Blache Jean Sébastien
Mummery Christine L
Moolenaar Wouter H
Jonkers Jos
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.02419-05
Published
2006-07-00
Pages
5015-22
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1489177
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.02419-05 PMC Full Text View journal details
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