Phospholipase C (PLC)-mediated hydrolysis of the limited pool of plasma membrane (PM) phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] requires replenishment from a larger pool of phosphatidylinositol (PtdIns) via sequential phosphorylation by PtdIns 4-kinases and phosphatidylinositol 4-phosphate (PtdIns4P) 5-kinases. Since PtdIns is synthesized in the endoplasmic reticulum (ER) and PtdIns(4,5)P2 is generated in the PM, it has been postulated that PtdIns transfer proteins (PITPs) provide the means for this lipid transfer function. Recent studies identified the large PITP protein, Nir2 as important for PtdIns transfer from the ER to the PM. It was also found that Nir2 was required for the transfer of phosphatidic acid (PtdOH) from the PM to the ER. In Nir2-depleted cells, activation of PLC leads to PtdOH accumulation in the PM and PtdIns synthesis becomes severely impaired. In quiescent cells, Nir2 is localized to the ER via interaction of its FFAT domain with ER-bound VAMP-associated proteins VAP-A and–B. After PLC activation, Nir2 also binds to the PM via interaction of its C-terminal domains with diacylglycerol (DAG) and PtdOH. Through these interactions, Nir2 functions in ER–PM contact zones. Mutations in VAP-B that have been identified in familial forms of amyotrophic lateral sclerosis (ALS or Lou-Gehrig's disease) cause aggregation of the VAP-B protein, which then impairs its binding to several proteins, including Nir2. These findings have shed new lights on the importance of non-vesicular lipid transfer of PtdIns and PtdOH in ER–PM contact zones with a possible link to a devastating human disease.
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Scanning electron micrograph of a cell from the endosperm of a barley grain. The cell is tightly packed with large, disk-shaped (A-type) and much smaller, almost spherical (B-type) starch granules. The smooth areas in this image are the surface of the cell walls of neighbouring endosperm cells. For further details see pp. 157-163. Image kindly provided by Elaine Barclay and Vasilios Andriotis (John Innes Centre, Norwich). - PDF Icon PDF LinkTable of Contents
Review Article|
February 09 2016
Phosphatidylinositol and phosphatidic acid transport between the ER and plasma membrane during PLC activation requires the Nir2 protein
Yeun Ju Kim;
Yeun Ju Kim
*Section on Molecular Signal Transduction, Program for Developmental Neuroscience, Eunice Kennedy Shriver NICHD, National Institutes of Health, Bethesda, MD 20892, U.S.A.
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Maria Luisa Guzman-Hernandez;
Maria Luisa Guzman-Hernandez
*Section on Molecular Signal Transduction, Program for Developmental Neuroscience, Eunice Kennedy Shriver NICHD, National Institutes of Health, Bethesda, MD 20892, U.S.A.
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Eva Wisniewski;
Eva Wisniewski
*Section on Molecular Signal Transduction, Program for Developmental Neuroscience, Eunice Kennedy Shriver NICHD, National Institutes of Health, Bethesda, MD 20892, U.S.A.
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Nicolas Echeverria;
Nicolas Echeverria
*Section on Molecular Signal Transduction, Program for Developmental Neuroscience, Eunice Kennedy Shriver NICHD, National Institutes of Health, Bethesda, MD 20892, U.S.A.
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Tamas Balla
Tamas Balla
1
*Section on Molecular Signal Transduction, Program for Developmental Neuroscience, Eunice Kennedy Shriver NICHD, National Institutes of Health, Bethesda, MD 20892, U.S.A.
1To whom correspondence should be addressed (email ballat@mail.nih.gov).
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Publisher: Portland Press Ltd
Received:
November 02 2015
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2016 Authors; published by Portland Press Limited
2016
Biochem Soc Trans (2016) 44 (1): 197–201.
Article history
Received:
November 02 2015
Citation
Yeun Ju Kim, Maria Luisa Guzman-Hernandez, Eva Wisniewski, Nicolas Echeverria, Tamas Balla; Phosphatidylinositol and phosphatidic acid transport between the ER and plasma membrane during PLC activation requires the Nir2 protein. Biochem Soc Trans 15 February 2016; 44 (1): 197–201. doi: https://doi.org/10.1042/BST20150187
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