Lecture 1 - Five lectures on intracellular protein...

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1 Five lectures on intracellular protein transport 1. Not comprehensive 2. We will try to concentrate on: How were things fgured out? What are the mechanisms? (Forget about names!) What is unknown? (cool projects For you to work on!) 3. Ask questions during the lecture (I’ll have breaks For them) or e-mail: tom_rapoport@hms.harvard.edu Introduction Reminder: each eukaryotic cell has different membrane- bound compartments
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2 General rule: Organelles are generated from the same type of organelle (similar to “omni cellula e cellula” (R. Virchow) Omni cellula e cellula (cells are only generated from cells) Rudolf Virchow Mathias Schleiden Theodor Schwann mitochondria mitochondria chloroplasts chloroplasts endoplasmic reticulum (ER) endoplasmic reticulum (ER) growth division nucleus nucleus
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3 Consequence: during cell division, each daughter cell needs at least one copy of each organelle Different strategies: Nucleus: very precise division and distribution Mitochondria: sufFcient numbers, random distribution ER: network is teared apart (perhaps also vesiculation) But, not so clear for Golgi or peroxisomes: could be generated from ER ±or Golgi: two different ideas: 1. Golgi fragments during mitosis, then reforms from fragments 2. Golgi is absorbed into ER during mitosis, then reforms During zygote formation from gamete cells: Egg brings cytosol and all organelles Sperm brings only nucleus All cytoplasmic organelles are derived from mother! (only easily seen with DNA containing organelles, such as mitochondria) Organelles have characteristic shapes Some organelles are more or less spheres e.g. peroxisomes, endosomes, lysosomes, secretory granules Some organelles consist of sheets e.g. Golgi stacks, inner and outer nuclear membrane, mitochondrial christae Some organelles consist of tubules particularly the ER network, but ER also has sheets How is the shape of an organelle brought about and maintained?
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4 Each organelle is characterized by a specifc set oF proteins General rule: every protein is found at only one location (except when en route to its Fnal destination) Most organelles have luminal and membrane proteins (exception: Golgi has no luminal proteins!) Lipids are also localized (although usually not in an absolute manner): Cholesterol: high in plasma membrane, low in the ER (although it is synthesized in the ER!) Phospho- inositides: different forms in different organelles (e.g. PI3P in endosomes, PI4,5P 2 in plasma membrane, PI3,5P 2 in lysosomes) Cardiolipin: mitochondria How does each organelle receive its specific set of lipids and proteins? Lipid transport Protein transport Lipid transport is still mysterious Questions: How is cholesterol transported? Probably not in vesicles
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Lecture 1 - Five lectures on intracellular protein...

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