PgmNr Y529: The lysine acetyltransferase complex NuA4 regulates cellular phosphatidylinositol-4-phospahate and phospholipid metabolism.

Authors:
L. Dacquay; M. Kennedy; A. Flint; J. Butcher; A. Stinzi; K. Baetz


Institutes
Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Canada.


Keyword: Signal Transduction

Abstract:

Understanding the regulation of phosphatidylinositol-4-phospahate (PI-4-P) homeostasis is important due to its critical roles in trafficking and proliferation. In Saccharomyces cerevisiae, the conserved lipid-binding proteins Sec14 and Osh4 regulate Golgi-localized PI-4-P homeostasis by either increasing or decreasing its levels respectively. It remains poorly understood how cells compensate in response to changes in the steady-state levels of PI-4-P. Our recent findings suggest that lysine acetyltransferase (KAT) regulation of transcription are contributing to the cellular response to PI-4-P deficiencies. Through a systematic analysis of all KAT deletion mutants, we found that mutants of the NuA4 KAT complex, including eaf1, are hypersensitive to SEC14 inactivation and OSH4 overexpression, two conditions where Golgi PI-4-P levels are depleted. Through transcriptome profiling, we determined that in PI-4-P deficient conditions, NuA4 regulates the transcription of the essential genes CDS1, which catalyzes CDP-DAG biosynthesis, and BCP1, which regulates the localization of the PI-4,5-P2 kinase Mss4. Genetic analysis and microscopy analysis confirms that NuA4-dependent regulation of CDS1 and BCP1 is essential to compensate for defects in Sec14 and decreases in PI-4-P. Altogether, we have discovered a new role for the lysine acetyltransferase NuA4 as a regulator of PI-4-P and phospholipid metabolism.



Yeast Database Genetic Index
1. gene symbol: SEC14; systematic name: YMR079W
2. gene symbol: OSH4; systematic name: YPL145C
3. gene symbol: CDS1; systematic name: YBR029C
4. gene symbol: BCP1; systematic name: YDR361C
5. gene symbol: EAF1; systematic name: YDR359C