VAC14 Nucleates a Protein Complex Essential for the Acute Interconversion of PI3P and PI(3,5)P2 in Yeast and Mouse

VAC14 Nucleates a Protein Complex Essential for the Acute Interconversion of PI3P and PI(3,5)P2 in Yeast and Mouse

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VAC14 Nucleates a Protein Complex Essential for the Acute Interconversion of PI3P and PI(3,5)P2 in Yeast and Mouse

dc.contributor.author	Jin, Natsuko
dc.contributor.author	Chow, Clement Y
dc.contributor.author	Zolov, Sergey N
dc.contributor.author	Davisson, Muriel
dc.contributor.author	Petersen, Jason L
dc.contributor.author	Zhang, Yanling
dc.contributor.author	Park, Sujin
dc.contributor.author	Duex, Jason E
dc.contributor.author	Goldowitz, Daniel
dc.contributor.author	Meisler, Miriam H
dc.contributor.author	Weisman, Lois S
dc.contributor.author	Liu, Li
dc.contributor.author	Bronson, Roderick Terry
dc.date.accessioned	2011-10-25T14:31:23Z
dc.date.issued	2008
dc.identifier.citation	Jin, Natsuko, Clement Y. Chow, Li Liu, Sergey N. Zolov, Roderick Bronson, Muriel Davisson, Jason L. Petersen, et al. 2008. VAC14 nucleates a protein complex essential for the acute interconversion of PI3P and PI(3,5)P in yeast and mouse. The EMBO Journal 27(24): 3221-3234.	en_US
dc.identifier.issn	0261-4189	en_US
dc.identifier.uri	http://nrs.harvard.edu/urn-3:HUL.InstRepos:5311764
dc.description.abstract	The signalling lipid PI(3,5)P2 is generated on endosomes and regulates retrograde traffic to the trans-Golgi network. Physiological signals regulate rapid, transient changes in PI(3,5)P2 levels. Mutations that lower PI(3,5)P2 cause neurodegeneration in human patients and mice. The function of Vac14 in the regulation of PI(3,5)P2 was uncharacterized previously. Here, we predict that yeast and mammalian Vac14 are composed entirely of HEAT repeats and demonstrate that Vac14 exerts an effect as a scaffold for the PI(3,5)P2 regulatory complex by direct contact with the known regulators of PI(3,5)P2: Fig4, Fab1, Vac7 and Atg18. We also report that the mouse mutant ingls (infantile gliosis) results from a missense mutation in Vac14 that prevents the association of Vac14 with Fab1, generating a partial complex. Analysis of ingls and two additional mutants provides insight into the organization of the PI(3,5)P2 regulatory complex and indicates that Vac14 mediates three distinct mechanisms for the rapid interconversion of PI3P and PI(3,5)P2. Moreover, these studies show that the association of Fab1 with the complex is essential for viability in the mouse.	en_US
dc.language.iso	en_US	en_US
dc.publisher	Nature Publishing Group	en_US
dc.relation.isversionof	doi:10.1038/emboj.2008.248	en_US
dc.relation.hasversion	http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2600653/pdf/	en_US
dash.license	LAA
dc.title	VAC14 Nucleates a Protein Complex Essential for the Acute Interconversion of PI3P and PI(3,5)P2 in Yeast and Mouse	en_US
dc.type	Journal Article	en_US
dc.description.version	Version of Record	en_US
dc.relation.journal	The EMBO Journal	en_US
dash.depositing.author	Bronson, Roderick Terry
dc.date.available	2011-10-25T14:31:23Z
dash.affiliation.other	HMS^Pathology	en_US