Loss of Vac14, a regulator of the signaling lipid phosphatidylinositol 3,5-bisphosphate, results in neurodegeneration in mice.
Proc Natl Acad Sci U S A
; 104(44): 17518-23, 2007 Oct 30.
Article
em En
| MEDLINE
| ID: mdl-17956977
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Fosfatos de Fosfatidilinositol
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Peptídeos e Proteínas de Sinalização Intracelular
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Degeneração Neural
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article