Endocytosis

What is taken up:

- Nutrients

- Signals

- Antibodies

- Enzymes

- Viruses

- Bacteria

- Membrane

Pathogens such as viruses invade endocytic pathways in order to get into the cell membrane so they can replicate.

Viruses have been used as tools to understand these pathways.

Some endocytosed material will eventually end up in the lysosome (nutrients), some will be recycled, and some will be taken up on one side of the cell and transported out of the apical membrane- process known as trans cytosis (antibodies)

There are multiple endocytic pathways

1. Macropinocytosis

2. Phagocytosis

3. Endocytosis

***Phagocytosis***= uptake of large particles

- bacteria, apoptotic cells

- removes cellular debris

- Pathogens are coated by antibodies before uptake (opsonisation)

- bacteria covered in antibodies interact with cell membrane, allowing the phagocyte to surround it

- yeast cells are taken up by phagocytosis by Dictyostelium

Frustrated phagocytosis= Fusion of the ruffles is cell autonomous, meaning it has to happen in just one cell.

Phagocytosis has been helpful for understanding membrane recycling

- The first find that membrane recycling occurs was found by a study where macrophages phagocytosed 1.1 micro metre late beads

- By counting the beads, researchers could estimate how much membrane was internalised

- The result was that 30% of total surface area was internalised per hour but there was no change in cell size, therefore the membrane must have been recycled

***Macropinocytosis**

- Cells form actin driven ruffles which can fuse to form macropinosomes

- Similar to phagocytosis in terms of mechanisms

- Non selective uptake of extracellular material

- Used by cancer cells to uptake nutrients

- Abundant in the immune system

Clathrin mediated endocytosis

Coated pits and vesicles are coated with Clathrin

Hypercholestoremia- too much cholesterol

- Studies found that patients with this disease have a mutation in the gene which codes for proteins that are involved in transport of cholesterol in cells.

- Mutations effect ability to take up LDL (Low density lipoproteins)

- Some patients receptors were unable to cluster, other patients didn't have LDL receptors, so there is nothing for LDL to bind to

Research by Brown and Goldstein into Familial hypercholestoremia

Dynamin is required to pinch off clathrin coated vesicles

***Gradient of pH is key for function on the endocytic pathway***

pH gradient decreases as you go down endosomal maturation from top to bottom

The lysosome has a pH of 4.5

Over expression of Rab5 results in enlarged endosomes

***Multi vesicular bodies*** are late endosomes with lots of intraluminal vesicles

The final stage of the endocytic pathway occurs at the lysosomes: Hydrolyses and lipases