Final Topic 21 - Protein Sorting and Endocytosis Flashcards
Virtually all proteins are synthesized in
The cytoplasm
Some proteins contain
Signal sequence
Proteins that are targeted to organelles must be able to
cross the membrane
Three mechanisms to cross the membrane
- Nuclear Pore Complex (only for nuclear proteins)
- Protein Translocators (ER, golgi, mitochondria)
- Vesicles - fuse with organelles
Proteins that are targeted to other organelles contain a
Signal sequence
Typically 15-60 amino acids long and is usually removed after the protein has reached it destination
Signal Sequence
The signal sequence is ___________ and ____________ to target a protein to the destination
Necessary and Sufficient
The nucleus is surrounded by a
Nuclear envelope
Contains a double membrane
Nuclear envelope
The nucleus contains
Nuclear pore complex
A large multi-protein assembly that forms a channel through the nuclear envelope
The nuclear pore complex
Proteins destined for the nucleus contain
A nuclear localization sequence (NLS)
Nuclear import requires
Cargo protein, Nuclear localization sequence, Nuclear transport receptor, Ran
Protein destined for the nucleus
Cargo protein
R and K amino acids
Nuclear localization sequence
Binds the NLS containing protein
Nuclear transport receptor
GTP binding protein that is involved in releasing cargo protein
Ran
Nuclear Import Process
- Nuclear transport receptor binds to the NLS
- Cargo protein and nuclear transport receptor move into the nucleus
- Ran-GTP (active form of the protein) Binds to nuclear transport receptor and releases cargo protein
- Ran-GTP/nuclear transport receptor move out of the nucleus
- Ran-GTP hydrolyzes GTP–>GDP + Pi and releases the nuclear transport receptor
The entry point for proteins destined for the golgi, lysosome, and the plasma membrane
ER
In order for proteins to get into the ER, they must pass through
The ER membrane
Proteins destined for the ER contain
An N-terminal ER signal sequence
A stretch of 8 or more hydrophobic amino acids
ER signal sequence
Proteins that enter the ER being to be translocated at
The same time they are synthesized
Being translocated at the same time they are synthesized requires that the ribosome be
Bound to the ER plasma membrane
Steps of Protein Import into the ER
- An ER signal sequence is exposed on the N-terminus of the growing polypeptide (in the cytoplasm)
- A signal-recognition particle (SRP) binds to the ER signal sequence
- A SRP receptor, embedded in the ER membrane, binds to the complex
- After binding, the SRP is release. The SRP receptor directs the complex to a translocation channel
- Once attached to the translocation channel, protein synthesis resumes
Stops translation and directs the complex to the ER membrane
Signal-recognition particle (SRP)
Two main types of Endocytosis
- Pinocytosis
2. Phagocytosis
The ingestion of fluid molecules by small vesicles
Pinocytosis
Cellular drinking
Pinocytosis
Undergo Pinocytosis
All eucaryotic cells
The ingestion of very large particles, such as organisms or cellular debris
Phagocytosis
Undergo Phagocytosis
Only certain phagocytic cells
One form of pinocytosis
Receptor-mediated endocytosis
Uses receptors that bind to specific molecules in the extracellular fluid
Receptor-mediated endocytosis
Endocytose the receptor/macromolecule complex
Clathrin coated vesicles
The cell uses ______________ to endocytose the receptor/macromolecule complex
Clathrin coated vesicles
A protein that forms a multi-protein assembly like a “cage” around a vesicle
Clathrin
During receptor mediated endocytosis:
- A receptor binds to some cargo protein
- Adaptin then binds to the receptor
- Clathrin binds to adaptin and the vessicles form
- The vesicle is cleaved from the membrane by Dynamin
- After the vesicle is released, clathrin and adptin disassemble (uncoat) from the vesicle
- The vesicle then fuses with the endosome
- The endosome sorts the receptor/cargo complex to the plasma membrane or the lysosome
A GTP-binding protein that hydrolyzes GTP to cut the membrane
Dynamin
Insoluble in the blood
cholesterol
Carried through the blood stream by binding to LDL
Cholesterol
LDL
Low-density lipoprotein (bad cholesterol)
HDL
High-density lipoprotein (good cholesterol)
Gell take up LDL to get cholesterol through RME by the
LDL receptor
The cholesterol in the cells is used in three ways:
- Goes to plasma membrane
- Is used to produce steroid hormones - cortisol
- Gets converted to bile acids - help digestion
4 mutations in the LDL receptor that cause Familial Hypercholesteremia
- Mutation of the synthesis of LDL receptor
- Mutation in the transport from ER to plasma membrane
- Mutation that disrupts binding to LDL
- Mutation in clustering in clathrin vesicle formation
Presence of high levels of cholesterol in the blood
Familial Hypercholesteremia
Mutations in the cytoplasmic domain of the LDL receptor causes
The clathrin/adaptin complex to fail to cluster around the receptor
How do we treat high cholesterol?
Statins and Fiber
Inhibit HMG-CoA reductase
Statin Drugs (Lipitor, etc)
Enzyme required for cholesterol biosynthesis
HMG-CoA reductase
Prevents the cells ability to recycle bile acid, forcing the cell to use cholesterol to make more bile acid
Fiber (Bile acid binding resin)
Create a cholesterol deficit inside the cell
Statins and fiber
Turns on the gene to produce more LDL receptors to take more cholesterol from the blood stream
Cholesterol deficit inside the cell
Increase LDL uptake efficiency and decrease LDL levels in the blood
More receptors