title: Loss of Vac14, a regulator of the signaling lipid phosphatidylinositol 3,5-bisphosphate, results in neurodegeneration in mice.
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)P(2) 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.
authors.affiliation: Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109-2216, USA.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Zhang
authors.forename: Sergey N
authors.initials: SN
authors.lastname: Zolov
authors.forename: Clement Y
authors.initials: CY
authors.lastname: Chow
authors.forename: Shalom G
authors.initials: SG
authors.lastname: Slutsky
authors.forename: Simon C
authors.initials: SC
authors.lastname: Richardson
authors.forename: Robert C
authors.initials: RC
authors.lastname: Piper
authors.forename: Baoli
authors.initials: B
authors.lastname: Yang
authors.forename: Johnathan J
authors.initials: JJ
authors.lastname: Nau
authors.forename: Randal J
authors.initials: RJ
authors.lastname: Westrick
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Morrison
authors.forename: Miriam H
authors.initials: MH
authors.lastname: Meisler
authors.forename: Lois S
authors.initials: LS
authors.lastname: Weisman
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D021381:Protein Transport; D015398:Signal Transduction
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018129:Phosphatidylinositol Phosphates; C525133:Vac14 protein, mouse; C106336:phosphatidylinositol 3,5-diphosphate