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Dynamics of Lipid Transfer by Phosphatidylinositol Transfer Proteins in Cells

Of many lipid transfer proteins identified, all have been implicated in essential cellular processes, but the activity of none has been demonstrated in intact cells. Among these, phosphatidylinositol transfer proteins (PITP) are of particular interest as they can bind to and transfer phosphatidylino...

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Detalles Bibliográficos
Autores principales: Shadan, Sadaf, Holic, Roman, Carvou, Nicolas, Ee, Patrick, Li, Michelle, Murray-Rust, Judith, Cockcroft, Shamshad
Formato: Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2635478/
https://www.ncbi.nlm.nih.gov/pubmed/18636990
http://dx.doi.org/10.1111/j.1600-0854.2008.00794.x
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author Shadan, Sadaf
Holic, Roman
Carvou, Nicolas
Ee, Patrick
Li, Michelle
Murray-Rust, Judith
Cockcroft, Shamshad
author_facet Shadan, Sadaf
Holic, Roman
Carvou, Nicolas
Ee, Patrick
Li, Michelle
Murray-Rust, Judith
Cockcroft, Shamshad
author_sort Shadan, Sadaf
collection PubMed
description Of many lipid transfer proteins identified, all have been implicated in essential cellular processes, but the activity of none has been demonstrated in intact cells. Among these, phosphatidylinositol transfer proteins (PITP) are of particular interest as they can bind to and transfer phosphatidylinositol (PtdIns) – the precursor of important signalling molecules, phosphoinositides – and because they have essential functions in neuronal development (PITPα) and cytokinesis (PITPβ). Structural analysis indicates that, in the cytosol, PITPs are in a ‘closed’ conformation completely shielding the lipid within them. But during lipid exchange at the membrane, they must transiently ‘open’. To study PITP dynamics in intact cells, we chemically targeted their C95 residue that, although non-essential for lipid transfer, is buried within the phospholipid-binding cavity, and so, its chemical modification prevents PtdIns binding because of steric hindrance. This treatment resulted in entrapment of open conformation PITPs at the membrane and inactivation of the cytosolic pool of PITPs within few minutes. PITP isoforms were differentially inactivated with the dynamics of PITPβ faster than PITPα. We identify two tryptophan residues essential for membrane docking of PITPs.
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spelling pubmed-26354782009-02-10 Dynamics of Lipid Transfer by Phosphatidylinositol Transfer Proteins in Cells Shadan, Sadaf Holic, Roman Carvou, Nicolas Ee, Patrick Li, Michelle Murray-Rust, Judith Cockcroft, Shamshad Traffic Original Articles Of many lipid transfer proteins identified, all have been implicated in essential cellular processes, but the activity of none has been demonstrated in intact cells. Among these, phosphatidylinositol transfer proteins (PITP) are of particular interest as they can bind to and transfer phosphatidylinositol (PtdIns) – the precursor of important signalling molecules, phosphoinositides – and because they have essential functions in neuronal development (PITPα) and cytokinesis (PITPβ). Structural analysis indicates that, in the cytosol, PITPs are in a ‘closed’ conformation completely shielding the lipid within them. But during lipid exchange at the membrane, they must transiently ‘open’. To study PITP dynamics in intact cells, we chemically targeted their C95 residue that, although non-essential for lipid transfer, is buried within the phospholipid-binding cavity, and so, its chemical modification prevents PtdIns binding because of steric hindrance. This treatment resulted in entrapment of open conformation PITPs at the membrane and inactivation of the cytosolic pool of PITPs within few minutes. PITP isoforms were differentially inactivated with the dynamics of PITPβ faster than PITPα. We identify two tryptophan residues essential for membrane docking of PITPs. Blackwell Publishing Ltd 2008-10 2008-08-06 /pmc/articles/PMC2635478/ /pubmed/18636990 http://dx.doi.org/10.1111/j.1600-0854.2008.00794.x Text en © 2008 The Authors Journal compilation © 2008 Blackwell Munksgaard
spellingShingle Original Articles
Shadan, Sadaf
Holic, Roman
Carvou, Nicolas
Ee, Patrick
Li, Michelle
Murray-Rust, Judith
Cockcroft, Shamshad
Dynamics of Lipid Transfer by Phosphatidylinositol Transfer Proteins in Cells
title Dynamics of Lipid Transfer by Phosphatidylinositol Transfer Proteins in Cells
title_full Dynamics of Lipid Transfer by Phosphatidylinositol Transfer Proteins in Cells
title_fullStr Dynamics of Lipid Transfer by Phosphatidylinositol Transfer Proteins in Cells
title_full_unstemmed Dynamics of Lipid Transfer by Phosphatidylinositol Transfer Proteins in Cells
title_short Dynamics of Lipid Transfer by Phosphatidylinositol Transfer Proteins in Cells
title_sort dynamics of lipid transfer by phosphatidylinositol transfer proteins in cells
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2635478/
https://www.ncbi.nlm.nih.gov/pubmed/18636990
http://dx.doi.org/10.1111/j.1600-0854.2008.00794.x
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