TY - JOUR
T1 - Ptdins4P synthesis by PI4KIIIα at the plasma membrane and its impact on plasma membrane identity
AU - Nakatsu, Fubito
AU - Baskin, Jeremy M.
AU - Chung, Jeeyun
AU - Tanner, Lukas B.
AU - Shui, Guanghou
AU - Lee, Sang Yoon
AU - Pirruccello, Michelle
AU - Hao, Mingming
AU - Ingolia, Nicholas T.
AU - Wenk, Markus R.
AU - De Camilli, Pietro
PY - 2012/12
Y1 - 2012/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85047686708&partnerID=8YFLogxK
U2 - 10.1083/jcb.201206095
DO - 10.1083/jcb.201206095
M3 - Article
AN - SCOPUS:85047686708
SN - 0021-9525
VL - 199
SP - 1003
EP - 1016
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 6
ER -