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

doi:10.1073/pnas.0702275104

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

Journal article

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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, …

Proceedings of the National Academy of Sciences - PNAS, Vol.104(44), pp.17518-17523

10/30/2007

DOI: 10.1073/pnas.0702275104

PMCID: PMC2077288

PMID: 17956977

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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.

Signal Transduction

Animals

Gene Expression Regulation

Intracellular Signaling Peptides and Proteins - deficiency

Intracellular Signaling Peptides and Proteins - genetics

Intracellular Signaling Peptides and Proteins - metabolism

Mice

Mice, Knockout

Nerve Degeneration - genetics

Nerve Degeneration - metabolism

Nerve Degeneration - pathology

Phosphatidylinositol Phosphates - metabolism

Protein Transport

Details

Title: Subtitle: Loss of Vac14, a regulator of the signaling lipid phosphatidylinositol 3,5-bisphosphate, results in neurodegeneration in mice
Creators: Yanling Zhang
Sergey N Zolov
Clement Y Chow
Shalom G Slutsky
Simon C Richardson
Robert C Piper - University of Iowa, Molecular Physiology and Biophysics
Baoli Yang - University of Iowa, BioVentures Center
Johnathan J Nau
Randal J Westrick
Sean J Morrison
Miriam H Meisler
Lois S Weisman
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.104(44), pp.17518-17523
DOI: 10.1073/pnas.0702275104
PMID: 17956977
PMCID: PMC2077288
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Grant note: P50 DK052617 / NIDDK NIH HHS R01 NS064015 / NINDS NIH HHS P50 DK52617 / NIDDK NIH HHS R01 GM050403 / NIGMS NIH HHS T32 GM007544 / NIGMS NIH HHS R01 GM50403 / NIGMS NIH HHS R01 GM24872 / NIGMS NIH HHS R01 GM024872 / NIGMS NIH HHS T32 GM07544 / NIGMS NIH HHS
Language: English
Date published: 10/30/2007
Academic Unit: Molecular Physiology and Biophysics; BioVentures Center; Medicine Administration; Internal Medicine
Record Identifier: 9984213857602771

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