Zhang, Yanling, Zolov, Sergey N., Chow, Clement Y., Slutsky, Shalom G., Richardson, Simon C. ORCID: 0000-0002-7927-0649 , Piper, Robert C., Yang, Baoli, Nau, Johnathan J., Westrick, Randal J., Morrison, Sean J., Meisler, Miriam H. and Weisman, Lois S. (2007) Loss of Vac14, a regulator of the signaling lipid phosphatidylinositol 3,5-bisphosphate, results in neurodegeneration in mice. PNAS, 104 (44). pp. 17518-17523. ISSN 1091-6490 (doi:https://doi.org/10.1073/pnas.0702275104)

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Abstract

The signaling lipid, phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2), 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)P2, is critical for the survival of neural cells.

Item Type:	Article
Additional Information:	[1] First published online: 23 October 2007. [2] Published in print: 30 October 2007. [3] This article is freely available online through the PNAS open access option. See: http://www.pnas.org/site/subscriptions/open-access.xhtml
Uncontrolled Keywords:	endocytosis, cell biology, Fab1, PIKfyve, PtdInsI(3,5)P2, spongiform, endosomal traffic
Subjects:	Q Science > QH Natural history > QH301 Biology R Medicine > RS Pharmacy and materia medica
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science > School of Science (SCI)
Related URLs:	Publisher Publisher Organisation
Last Modified:	06 Nov 2020 11:23
URI:	http://gala.gre.ac.uk/id/eprint/4256

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