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

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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

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