Phosphatidylinositol 4-Phosphate Formation at ER Exit Sites Regulates ER Export

Department of Cell Biology, University of Pittsburgh School of Medicine, 3500 Terrace Street, Pittsburgh, Pennsylvania 15261, USA.
Developmental Cell (Impact Factor: 9.71). 12/2006; 11(5):671-82. DOI: 10.1016/j.devcel.2006.09.001
Source: PubMed


The mechanisms that regulate endoplasmic reticulum (ER) exit-site (ERES) assembly and COPII-mediated ER export are currently unknown. We analyzed the role of phosphatidylinositols (PtdIns) in regulating ER export. Utilizing pleckstrin homology domains and a PtdIns phosphatase to specifically sequester or reduce phosphorylated PtdIns levels, we found that PtdIns 4-phosphate (PtsIns4P) is required to promote COPII-mediated ER export. Biochemical and morphological in vitro analysis revealed dynamic and localized PtsIns4P formation at ERES. PtdIns4P was utilized to support Sar1-induced proliferation and constriction of ERES membranes. PtdIns4P also assisted in Sar1-induced COPII nucleation at ERES. Therefore, localized dynamic remodeling of PtdIns marks ERES membranes to regulate COPII-mediated ER export.

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    • "Thus, PI4KA is mainly found in the endoplasmic reticulum (ER). Its activity seems to regulate both the formation of ER exit sites [15,16] and the concentration of PtdIns4P in the plasma membrane [17]. PtdIns4P is a precursor of other phosphoinositides (PIs), generated by additional phosphorylation(s), involved in a wide range of cellular functions [18]. "
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    • "In these distinct zones of the ER, a set of cytoplasmic proteins, collectively known as the COPII coat, generates COPII vesicles through a sequence of events under the control of multiple regulatory mechanisms (Aridor and Balch, 2000; Lee and Linstedt, 2000; Blumental-Perry et al., 2006; Yamasaki et al., 2006; Higashio et al., 2008; Rismanchi et al., 2009; Kodera et al., 2011; Yorimitsu and Sato, 2012; Yoshibori et al., 2012). The COPII coat is responsible for the direct or indirect capture of cargo proteins and for the physical deformation of the ER membrane that drives the COPII vesicle formation. "
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    • "Recent studies suggested that PI(4)P plays an important role in membrane trafficking from the ER to the Golgi [26] [29] [30]. Our in vitro lipid overlay and liposome sedimentation assays showed that KIAA0725p interacts with three PIPs, i.e. "
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