VAC14 Nucleates a Protein Complex Essential for the Acute Interconversion of PI3P and PI(3,5)P2 in Yeast and Mouse
View/ Open
Author
Jin, Natsuko
Chow, Clement Y
Zolov, Sergey N
Davisson, Muriel
Petersen, Jason L
Zhang, Yanling
Park, Sujin
Duex, Jason E
Goldowitz, Daniel
Meisler, Miriam H
Weisman, Lois S
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1038/emboj.2008.248Metadata
Show full item recordCitation
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.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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2600653/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:5311764
Collections
- HMS Scholarly Articles [17922]
Contact administrator regarding this item (to report mistakes or request changes)