Transcript Molecular Biology of the Cell

Chapter 8
Intracellular Compartments and
Protein Sorting: Transport
Between the Nucleus and the
Cytosol
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Relative Volumes Occupied by the Major Intracellular Compartments in
a Liver Cell
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Relative Amounts of Membrane Types in Two Kinds of Eukaryotic Cells
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Some Signal Sequences
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• Inner Nuclear Membrane
• Outer Nuclear Membrane
• Bidirectional Traffic
– Histones, DNA and RNA polymerases, gene regulatory
proteins, RNA processing proteins are all selectively imported
into the nuclear compartment from the cytosol
– tRNAs, mRNAs are exported to the cytosol.
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Nuclear Pore Complexes Perforate the Nuclear Envelope
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Side view of two NPCs; note that the inner and outer nuclear
membranes are continuous at the edges of the pore.
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Gated Diffusion Barrier of the NPC
Meshwork blocks passive diffusion of large
macromolecules.
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Importing of Proteins to the Nucleus
• When nuclear proteins are extracted from the nucleus, then put
into the cytosol, they find their way back to the nucleus.
– Nuclear Localization Signals
– How could you experimentally figure this out? That is, how
could you even determine there was a nuclear localization
signal?
– Signals are short sequences rich in lysine and arginine and can
be located just about anywhere on the protein.
• Nuclear localization signals are recognized by nuclear import
receptors.
– Soluble in the cytosol and bind to both the signal on the protein
to be transported and to the NPC proteins.
– Fibrils
– Hop through by repeated binding and dissociating and
rebinding.
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Nuclear import receptors are specific to the signal proteins
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Nuclear Export
• Large molecules such as rRNA subunits and RNA molecules are
also selectively transported.
• Nuclear Export Signals on these macromolecules.
• Nuclear Export Receptors: bind to both signal and the NPC
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Access to the Transport Machinery
• Some proteins that transport molecules out of the nucleus also
have nuclear localization signals.
• They are continually shuttled back and forth.
• Rate of import > rate of export then the protein is mostly located
in the nucleus.
• Remember these localization signals control the flow of the
protein, in and out of the nucleus. These signals are turned on and
off by phosphorylation and amino acids close to the signal
sequences.
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Peroxisomes
Bounded by single membrane
No DNA or ribosomes
Selective import
Presence of catalase
High usage of oxygen: may have
been an ancient organelle that
allowed cells to tolerate the
beginnings of an oxygen
environment.
Present day functions would be
those that have not been taken
over by mitochondria.
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Peroxisomes Use Molecular Oxygen and Hydrogen
Peroxide to Perform Oxidation Reactions
• Catalase uses the hydrogen peroxide to oxidize a variety of
substrates.
– Liver and Kidney Cells where detox occurs.
– 25% of any alcohol you drink is oxidized to acetaldehyde.
– If excess hydrogen peroxide accumulates, catalase converts it
to water and oxygen as we saw in the enzyme lab.
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• Breakdown of fatty acids
– Beta Oxidation
• Acetyl CoA
– Which then must be transported out to be used in
other reactions.
• In mammalians, beta oxidation occurs in mitochondria and
peroxisomes.
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Biosynthesis of Plasmalogens
Phospholipids in myelin.
Myelin deficiencies of the axons
Peroxisome disorders lead to neurological
disorders.
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Not Plants Too???!!! Where they are called
glyoxysomes.
Seeds and fatty acids.
Animals cannot convert fatty acids to
carbohydrates
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• Import of Proteins Into Peroxisomes
– Shorts signal sequence of 3 amino acids can be at either end of
the protein, the C- terminus or the N-terminus.
– Soluble receptor proteins in the cytosol
– Docking proteins on the peroxisome surface.
– Requires ATP.
– Zellweger Syndrome
• Import process is dysfunction leading to empty
peroxisomes causing abnormalities in the brain, liver and
kidneys and thus die soon after birth.
• One form of the syndrome is caused by a mutation in a
gene coding for a peroxisomal integral membrane protein
involved in import.
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And From Where Do These Rascals Arise? Still debated
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