2. Academic Validation
  3. The autotaxin-LPA axis promotes membrane trafficking and secretion in yolk sac visceral endoderm cells

The autotaxin-LPA axis promotes membrane trafficking and secretion in yolk sac visceral endoderm cells

  • Biol Open. 2023 Oct 5:bio.060081. doi: 10.1242/bio.060081.
Seiichi Koike 1 2 3,  Kazuko Keio-Masu 1 2,  Yoko Tanimoto 4,  Satoru Takahashi 4,  Masayuki Masu 1 2
Affiliations

Affiliations

  • 1 Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
  • 2 Department of Molecular Neurobiology, Institute of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
  • 3 Laboratory of Organelle Synthetic Biology, Graduate School of Science and Engineering for Research, University of Toyama, 3190 Gofuku, Toyama-shi, Toyama 930-855, Japan.
  • 4 Laboratory Animal Resource Center and Transborder Medical Research Center, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
PMID: 37795611 DOI: 10.1242/bio.060081
Abstract

Autotaxin, encoded by the Enpp2 gene, is an exoenzyme that produces lysophosphatidic acid, thereby regulating many biologic functions. We previously reported that Enpp2 mRNA was abundantly expressed in yolk sac visceral endoderm (VE) cells and that Enpp2-/- mice were lethal at embryonic day 9.5 owing to angiogenic defects in the yolk sac. Enpp2-/- mice showed lysosome fragmentation in VE cells and embryonic abnormalities including allantois malformation, neural tube defects, no axial turning, and head cavity formation. However, whether the defects in endocytic vesicle formation affect membrane trafficking in VE cells remained to be directly examined. In this study, we found that pinocytosis, transcytosis, and secretion of angiogenic factors such as vascular endothelial growth factor and transforming growth factor β1 were impaired in Enpp2-/- VE cells. Moreover, pharmacologic inhibition of membrane trafficking phenocopied the defects of Enpp2-/- mice. These findings demonstrate that Enpp2 spromotes endocytosis and secretion of angiogenic factors in VE cells, thereby regulating angiogenesis/vasculogenesis and embryonic development.

Keywords

Autotaxin; Endocytosis; Mouse; Secretion; Visceral endoderm; Yolk sac.

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