Briefly summarize the LDL receptor-mediated endocytosis process?
LDL binds to receptors proteins
by endocytosis, the membrane pinches in, into a vesicle coated with clathrin
The clathrin-coated vesicle uncoats so that the now uncoated vesicle can fuse with another vesicle, usually an endosome.
The endosome will fuse with primary lysosomes, whose hydrolytic enzymes are present
The receptors are recycled back to the membrane and the cholesterol becomes free in th eblood
Explain the transferrin cycle.
Ferrotransferrin (transferrin bearing an iron molecule) binds to a transferrin receptor.
A coated vesicle (with clathrin) forms. The vesicle then becomes uncoated.
After uncoating, the vesicle fuses with an endosome.
The acidity of the endosomal environment causes the iron to be released from the transferrin, which is now called apotransferrin. Iron is released into the bloodstream.
Apotransferrin is recycled to the cell surface, where it dissociates from the receptor due ot the neutral pH.
The transferrin process is __ dependent.
After endocytosis, __ is released from the __ in the __. The iron dissociates and remains in the cell. The __ remains bound to its receptor at this __, and they cycle to the cell surface together. When the __ encounters the __ of the exterior medium, the __ is released to gather its next load of iron.
the process of moving something from side of the cell to the other
(example: how antibodies get moved from the mom's bloodstream to the fetus)
What is the major mechanical force that causes the pit to form?
forming the lattice (polymeration)
Why does (or how does) clathrin bind to the membrane?
other proteins are involved because clathrin won't bind to the membrane itsel
What is the structure of clathrin?
Explain the triskelion structure.
How do they fit together.
each arm is made of a heavy and a light chain (basic structure)
the way they fit together with another clathrin molecule is a way that forms a lattice (hexagonal kind of shape)
material can be stored in cell and taken in by receptor mediated endocytosis
fate: long-term storage
eventually, the material will be broken down
__ bind on the inner side of the membrane.
How many lipids involved? Which one?
What does it do?
PIP2 membrane lipid that has been phosphorylated
- binds proteins, assembly particles, etc. to the membrane
on one side, it'll bind to the membrane. On the other side, it'll bind clathrin
only in brain cells
may fiunction as an assembly particle
One of the things that these assemblies bind to are __. They can...
help detect which receptors will be involved in pits
True or False:
there are not many assembly molecules
each made of a complex of proteins called adaptor proteins and usually about four different kinds
found bound to both clathrin (on one side) and the membrane (on the other)
there is a space between the clathrin lattice and the membrane (20 nm)
What do these proteins do?
promote clathrin to form into the lattice and promote it
Receptors that bind to the assembly particles have what?
very specific ctosolic domains
If there is no signal for a receptor to bind, it will be __. What varies is the __ that determines involvement in pits.
excluded from the pit
__ is the main mechanical force that caues the pt to form. It is facilitated by __.
assembly of clathrin
binds to PIP2 in the membrane
goes all the way around
molecules of dynamin are polymerizing around the neck
Uses GTP to sever the membrane
GTP is hydrolyzed and the energy is used
it is a cytosolic protein (components found in cytosol); 900 amino acids; absolutely essential
What causes detachment of the vesicle from the membrane?
dynamin by severing the vesicle from membrane
Briefly describe a clathrin coated pit formation.
clathrine lattice formation and budding is regulated by AP-2, AP180, and epsin
Vesicle scission regulated by dynamin
Cuncoating induced by PIP2 dephosphylation
The lipid __ is a principal player in the assembly of the molecular machinery that governs __. The __ of __, __ and __ to the plasma membrane results in __ and the __. __, recruited to the neck of the forming vesicle by binding to __, causes scission of the vesicle from the plasma membrane. The __ of vesicles are disassembled when __ dephosphorylates __, converting it to __.
clathrin lattice formation
budding of clathrin-coated vesicles
What are the three theories of the detachment of the vesicle from the membrane?
When GTP hydrolyzes to GDP, it causes dynamin to change shape and sever the vesicle
When GTP is hydrolyzed, dynamin changes shape, causing activation of effector protein to sever vesicle
When GTP is hydrolyzed, it causes dynamin to contract, severing the vesicle (no disassembly)
What is absolutely necessary for detachment of vesicle from teh membrane?
The __ of certain membrane proteins bind specificially to assembly particles that, in turn, bind to __ as it __ spontaneously over a region of membrane. Protens that do not bind to assembly particles are __ from these vesicles. __ then polymerizes over the neck of the pit; regulated by __, the neck pinches off, forming a __. __ initiates the process of vesicle budding.