Section 3.

Biogenesis, Traffic and

Functions of Cellular Membrane
Systems

Chapter 7. Endocytosis
Dr. Mirvat El-Sibai
 Endocytosis
- All eukaryotic cells use endocytosis to capture extracellular molecules by
enclosure within membrane vesicles

- Cells use endocytosis to maintain homeostasis and to defend themselves

- Endocytosis is divided into two categories:

- Phagocytosis: Cellular uptake of large particles into large phagosomes

White blood cells are the body “professional phagocytes”

- Pinocytosis: Cellular uptake of fluids and solutes into small pinocytic

vesicles
 Endocytosis

Most types of endocytosis involve the selective uptake of macromolecules

(ligands) that bind high affinity receptors and are then internalized

Ligands can be proteins, glycoproteins or carbohydrates

This is called receptor-mediated endocytosis

 Endocytic vesicles
1- Clathrin coated vesicles
2- Uncoated pinocytic vesicles
3- Caveolae
4- Macropinosomes
5- Phagosomes
 Phagocytosis

Phagocytosis in higher organisms is restricted to macrophages and

neutrophils, where it plays an important role in host defense against invading
pathogens
 Clathrin-dependent endocytosis
- Used by cells to obtain nutrients such as
iron and cholesterol

- Also referred to as receptor-mediated

endocytosis

- Occurs at specialized patches on the

plasma membrane called coated pits

- The underlying protein lattice of pits is

made of clathrin triskelions and adaptor
molecules

- Receptor-ligand complexes concentrate in

these patches, which pinch off forming
clathrin-coated vesicles
 Clathrin coats
- Clathrin is involved in forming vesicles
during endocytosis and from the TGN as
well
- Clathrin consists of 3 190-KD heavy
chains and 3 30-KD light chains
- The 3-legged structure of clathrin is
called triskelion

- APs (adaptor proteins) are also needed

to assemble the clathrin coats
- AP1, 2, 3 and 4 have been identified
- AP1 and 3 mediate trafficking out of
the TGN
- AP2 functions in endocytic coated
vesicles
1.THE SHAPE AND STRUCTURE OF PROTEINS
Protein Molecules Often Serve as Subunits for the
Assembly of Large Structures
Clathrin coats
 Receptor clustering into coated pits

- Endocytic receptors have internalization motifs on their cytoplasmic site

encoded in their sequence
- These are recognized by AP2
- The process of coat assembly is probably regulated by GTPases (this
remains unknown)
 Dynamin and coated vesicle budding

- Driven by clathrin assembly, the plasma membrane gains curvature,

forming a deeply invaginated coated pit
- This requires ATP, GTP and accessory proteins that remain unknown
- Dynamin is a GTPase that assembles into a collar at the neck of coated pits
and pinches the vesicle off
- Dynamin binds PIP2
 Receptor clustering into coated pits

- Soon after internalization, the vesicle sheds its coat

- This frees the vesicle to fuse with target endosomes
- The chaperone Hsc70 catalyzes the removal of clathrin in vitro