MCDB428Lect15 - MCDB 428 Lecture 15: Monday February 11,...

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Lecture 15: Monday February 11, 2008 Today’s Outline The phosphoinositide Family Description of PI and PI-isoforms PI-isoform family complement How PI-binding domains display specificity Where different PI-isoforms are distributed intracellularly Endocytosis Endocytosis versus Exocytosis Overview of the endocytic pathway Three routes to the lysosome Phagocytosis Receptor Mediated Endocytosis Ligand-receptor binding drives internalization Different types of pinocytosis Formation of caveolae Role of Caveolin Studying receptor-mediated endocytosis LDL receptor trafficking pathway Transferrin and ferrotransferrin trafficking Endosome to Lysosome Trafficking Sorting and recycling in the early endosome Maturation of the late endosome into lysosomes Formation of internal vesicles Role of ubiquitin and ESCRT proteins sorting MCDB 428
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Many Proteins Contain Phosphoinositide Binding Domains Ability to bind specific types of lipids helps ensure proteins bind in right place and at right time during membrane trafficking steps For example, dynamin only binds to the neck of a budding CCV due to local increases in PI-4,5P 2 , whereas SNX1 only bind to endosomes due to presence of PI-3P
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The Phosphoinositide Lipid Family PI and the various PIPs only comprise about 10% of the total lipids in biological membranes therefore considered “signaling” lipids rather than structural Presence of the inositol sugar headgroup defines this family of phospholipids and provides the basis of its role in regulating numerous aspects of membrane trafficking and signal transduction pathways The headgroup can be phosphorylated (or dephosphorylated) at any of the remaining five carbons in the inositol sugar ring The enzymes responsible for these various phosphorylation and dephosphorylation steps differ between distinct membrane compartments
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The Phosphoinositide Lipid Family
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PI-binding Domains Allow Discrimination Between Different PI Isoforms Left protein has a PI-3P binding domain, whereas right protein has a PI-4,5P2 binding domain Localized production of different PI isoforms allows recruitment of proteins to specific
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MCDB428Lect15 - MCDB 428 Lecture 15: Monday February 11,...

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