Loss of Vac14, a regulator of the signaling lipid phosphatidylinositol 3,5-bisphosphate, results in neurodegeneration in mice

Yanling Zhang, Sergey N. Zolov, Clement Y. Chow, Shalom G. Slutsky, Simon C. Richardson, Robert C. Piper, Baoli Yang, Johnathan J. Nau, Randal J. Westrick, Sean J. Morrison, Miriam H. Meisler, Lois S. Weisman

Research output: Contribution to journalArticlepeer-review

166 Scopus citations

Abstract

The signaling lipid, phosphatidylinositol 3,5-bisphosphate (PI(3,5)P 2), likely functions in multiple signaling pathways. Here, we report the characterization of a mouse mutant lacking Vac14, a regulator of PI(3,5)P2 synthesis. The mutant mice exhibit massive neurodegeneration, particularly in the midbrain and in peripheral sensory neurons. Cell bodies of affected neurons are vacuolated, and apparently empty spaces are present in areas where neurons should be present. Similar vacuoles are found in cultured neurons and fibroblasts. Selective membrane trafficking pathways, especially endosome-to-TGN retrograde trafficking, are defective. This report, along with a recent report on a mouse with a null mutation in Fig4, presents the unexpected finding that the housekeeping lipid, PI(3,5)P 2, is critical for the survival of neural cells.

Original languageEnglish (US)
Pages (from-to)17518-17523
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number44
DOIs
StatePublished - Oct 30 2007

Keywords

  • Endosomal traffic
  • Fab1
  • PIKfyve
  • PtdInsI(3,5)P
  • Spongiform

ASJC Scopus subject areas

  • General

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