Phosphatidylinositol 3,5-bisphosphate: Low abundance, high significance

Recent studies of the low abundant signaling lipid, phosphatidylinositol 3,5‐bisphosphate (PI(3,5)P2), reveal an intriguingly diverse list of downstream pathways, the intertwined relationship between PI(3,5)P2 and PI5P, as well as links to neurodegenerative diseases. Derived from the structural lipi...

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Bibliographic Details
Published in:BioEssays 2014-01, Vol.36 (1), p.52-64
Main Authors: McCartney, Amber J., Zhang, Yanling, Weisman, Lois S.
Format: Article
Language:English
Subjects:
5-bisphosphate
Amyotrophic lateral sclerosis
Animals
Fab1
Fig4
Humans
Mutation
Mutation - genetics
Neurodegenerative Diseases - genetics
Neurodegenerative Diseases - metabolism
phosphatidylinositol 3
phosphatidylinositol 3,5‐bisphosphate
Phosphatidylinositol Phosphates - genetics
Phosphatidylinositol Phosphates - metabolism
phosphoinositide lipid
PIKfyve
Signal Transduction - genetics
Vac14
Vac7
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Summary:Recent studies of the low abundant signaling lipid, phosphatidylinositol 3,5‐bisphosphate (PI(3,5)P2), reveal an intriguingly diverse list of downstream pathways, the intertwined relationship between PI(3,5)P2 and PI5P, as well as links to neurodegenerative diseases. Derived from the structural lipid phosphatidylinositol, PI(3,5)P2 is dynamically generated on multiple cellular compartments where interactions with an increasing list of effectors regulate many cellular pathways. A complex of proteins that includes Fab1/PIKfyve, Vac14, and Fig4/Sac3 mediates the biosynthesis of PI(3,5)P2, and mutations that disrupt complex function and/or formation cause profound consequences in cells. Surprisingly, mutations in this pathway are linked with neurological diseases, including Charcot‐Marie‐Tooth syndrome and amyotrophic lateral sclerosis. Future studies of PI(3,5)P2 and PI5P are likely to expand the roles of these lipids in regulation of cellular functions, as well as provide new approaches for treatment of some neurological diseases. Phosphatidylinositol 3,5‐bisphosphate (PI(3,5)P2), a low abundance phospholipid, regulates many cellular pathways. A protein complex that includes Fab1/PIKfyve, Vac14, and Fig4/Sac3 synthesizes PI(3,5)P2. Mutations in the Fab1/PIKfyve complex have profound effects in all organisms tested, and result in human diseases including Charcot‐Marie‐Tooth syndrome and amyotrophic lateral sclerosis.
ISSN:0265-9247
1521-1878
DOI:10.1002/bies.201300012