Biology 2382B Lecture Notes - Lecture 11: Ldl Receptor, Cholesteryl Ester, Transferrin Receptor
5 May 2018
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Lecture 06: Receptor-Mediated Endocytosis
- Endocytosis: Getting stuff outside of the cell to the inside
- Invagination of plasma membrane forms vesicles which undergo maturation steps to become late
endosomes and ultimately lysosomes, or it can be recycled back to plasma membranes.
How can Cells Internalize the Extracellular Materials?
- Phagocytosis macrophages engulf bacteria and digests it (occurs in specialized immune cells).
- Pinocytosis nonspecialized/nonselective, internalize small molecules, like sipping fluid from outside
- Receptor-Mediated Endocytosis a method of selective internalization of specific extracellular
molecules (ligands). Types of Ligand:
- LDL (low-density lipoprotein)
- Transferrin
- Hormones (e.g. insulin), Glycoproteins, etc.
Ligands
1) Low-Density Lipoprotein (LDL)
- Lipids are transported in large, well-defined, water-soluble complexes/particles called lipoproteins
- LDL contains approximately 88% cholesterol esters and mediates cholesterol transport
- LDL receptors on plasma membrane (localized in clathrin-coated pits)
- Binding of LDL to LDL receptors is mediated by Apolipoprotein B belt around the ball of fat.
- Amphipathic Shell composed of phospholipid monolayer
- Apolar Core that hydrophobic, mostly cholesteryl esters
1. LDL elt ids to LDL reeptor’s idig ar on plasma membrane *
2. APs recognize sorting signals of cargo proteins or receptors (NPXY) and then recruit Clathrin/triskelion
which accumulates on localized pit and forms a cage around vesicle (2 types of APs AP1 is the Trans-
Golgi, AP2 is the Plasma Membrane)
3. Clathrin-coated vesicles pinch off using dynamin and GTP hydrolysis (dynamin forms ring around
vesicle neck and polymerizes).
4. Clathrin-coated vesicle enters cell and clathrin coat is shed now called smooth early endosome
5. pH of endosome decreases**which dissociates LDL from its receptor due to low affinity (Ligand-
Binding arm (-ve residues) bind w/high affinity to +ve B-propellor domain instead which releases LDL
particle).
*How does the Cell recognize the LDL particles?
- It binds to the receptor! (pH-dependent binding).
- LDL receptor has 3 domains:
1. Short C-terminal cytosolic segment w/sorting signal.
2. Long N-terminal exoplasmic segment w/a ligand binding domain and a β-propeller domain.
3. Ligand Binding-Arm
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