Ptdins4P synthesis by PI4KIIIα at the plasma membrane and its impact on plasma membrane identity

Fubito Nakatsu, Jeremy M. Baskin, Jeeyun Chung, Lukas B. Tanner, Guanghou Shui, Sang Yoon Lee, Michelle Pirruccello, Mingming Hao, Nicholas T. Ingolia, Markus R. Wenk, Pietro De Camilli*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

217 Citations (Scopus)

Abstract

Plasma membrane phosphatidylinositol (PI) 4-phosphate(PtdIns4P) has critical functions via both direct interactions and metabolic conversion to PI 4,5-bisphosphate (PtdIns(4,5)P2) and other downstream metabolites. However, mechanisms that control this PtdIns4P pool in cells of higher eukaryotes remain elusive. PI4KIIIα,the enzyme thought to synthesize his PtdIns4P pool, is reported to localize in the ER, contrary to the plasma membrane localization of its yeast homologue, Stt4. In this paper, we show that PI4KIIIα was targeted to the plasma membrane as part of an evolutionarily conserved complex containing Efr3/rolling blackout, which we found was a palmitoylated peripheral membrane protein. PI4KIIIαknockout cells exhibited a profound reduction of plasma membrane PtdIns4P but surprisingly only a modest reduction of PtdIns(4,5)P2 because of robust up-regulation of PtdIns4P 5-kinases. In these cells, however, much of the PtdIns(4,5)P2 was localized intracellularly, rather than at the plasma membrane as in control cells, along with proteins typically restricted to this membrane, revealing a major contribution of PI4KIIIα to the definition of plasma membrane identity.

Original languageEnglish
Pages (from-to)1003-1016
Number of pages14
JournalJournal of Cell Biology
Volume199
Issue number6
DOIs
Publication statusPublished - Dec 2012
Externally publishedYes

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