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A Conserved, Lipid‐Mediated Sorting Mechanism of Yeast Ist2 and Mammalian STIM Proteins to the Peripheral ER
Author(s) -
Ercan Ebru,
Momburg Frank,
Engel Ulrike,
Temmerman Koen,
Nickel Walter,
Seedorf Matthias
Publication year - 2009
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/j.1600-0854.2009.00995.x
Subject(s) - microbiology and biotechnology , endoplasmic reticulum , biology , stim1 , protein targeting , integral membrane protein , phosphatidylinositol , membrane protein , peripheral membrane protein , golgi apparatus , biochemistry , signal transduction , membrane
Sorting of yeast Ist2 to the plasma membrane (PM) or the cortical endoplasmic reticulum (ER) requires a cortical sorting signal (CSS Ist2 ) that interacts with lipids including phosphatidylinositol‐4,5‐bisphosphate (PI(4,5)P 2 ) at the PM. Here, we show that the expression of Ist2 in mammalian cells resulted in a peripheral patch‐like localization without any detection of Ist2 at the cell surface. Attached to C‐termini of mammalian integral membrane proteins, the CSS Ist2 targeted these proteins to PM‐associated domains of the ER and abolished trafficking via the classical secretory pathway. The interaction of integral membrane proteins with PI(4,5)P 2 at the PM created ER–PM contacts. This process is similar to the regulated coupling of ER domains to the PM via stromal interaction molecule (STIM) proteins during store‐operated Ca 2+ entry (SOCE). The CSS Ist2 and the C‐terminus of the ER‐located Ca 2+ sensor STIM2 were sufficient to bind PI(4,5)P 2 and PI(3,4,5)P 3 at the PM, showing that an evolutionarily conserved mechanism is involved in the sorting of integral membrane proteins to PM‐associated domains of the ER. Yeast Ist2 and STIM2 share a common basic and amphipathic signal at their extreme C‐termini. STIM1 showed binding preference for liposomes containing PI(4,5)P 2 , suggesting a specific contribution of lipids to the recruitment of ER domains to the PM during SOCE.