Endocytosis

What contain acid hydrolases which can digest every type of biological molecule

lysosomes

The what pH optimum of these enzymes is maintained by a proton pump (H+-ATPase)

low

marker of aging

neurons

a mitochondrion and peroxisome enclosed in a double membrane wrapper

What is happening

Autophagy

autophagic vacuole (autophagosome) fuses with what

lysosome

uptake of macromolecules from extracellular fluid

Endocytosis

nonspecific uptake of extracellular fluids

Pinocytosis

uptake of specific extracellular ligands following their binding to receptors

Receptor-mediated endocytosis

uptake of large particulate matter (food, bacteria); specific to some cell types

Phagocytosis

Endocytic Pathway
• what is taken in from the extracellular space

Molecules

Endocytic Pathway
• What taken in from the plasma membrane and recycled back to the plasma membrane

Receptors

Endocytic Pathway
• Newly synthesized molecules coming from where and being sent to lysosomes

ER

Uptake of yolk lipoproteins by hen oocyte

Receptor-mediated endocytosis

Structure of coated pits due to structure of clathrin

LDL-cholesterol droplets on extracellular surface

Structure of coated pits due to structure of clathrin

Clathrin-containing polygons on inner surface of cell

Structure of coated pits due to structure of clathrin

Cytosolic surface showing invagination of clathrin coated pit.

Triskelions: # heavy chains + # light chains

3, 3

36 overlapping triskelions

Clathrin cage

Endocytosis from plasma membrane
Adaptor:

AP2 complex

from Trans Golgi Network to lysosome
Adaptor:

GGA

AP2 adaptor: # polypeptides; binds accessory proteins

4

interacts with cytoplasmic tails of receptors (bound to cargos)

μ chain

recruits clathrin

β-adaptin

recruits AP2 to the PM

PI(4,5)P2

cytosolic proteins but must be recruited to correct organelle when needed

Adaptors

phospholipids unique to the specific organelle

Adaptor recruitment

Adaptor proteins provide what at each membrane
– PM : AP2; TGN : GGA (lysosomal enzymes)

specificity

headgroups that interact with specific protein domains

Phosphoinositide phosphate lipids (PIPs)

PIs provide modifiable/customizable what profiles unique to different organelles

lipid

Several PI and PIP kinases/phosphatases are localized to different organelles where they what the production/removal of these lipid species

catalyze

forms helical collar (polymerizes)

Dynamin

twisting motion in the helix; membrane fission

GTP hydrolysis

ATPase Hsc70, recruited by what, is required to dissociate the clathrin coat

auxillin

Clathrin Coat Formation

Cargo selection and clathrin recruitment via what

adaptors

Clathrin Coat Formation

Pinching off from membrane via what

dynamin

Clathrin Coat Formation

Uncoating of clathrin coated vesicle requires what

ATPase

vesicles and tubules that transport vesicle-bound material

endosomes

-near cell periphery

- sort materials and sends bound ligands

Early endosomes

-near the nucleus
-known as multivesicular bodies (MVBs)

Late endosomes

What happens to endocytosed materials? lysosomal degradation of what and transmembrane proteins

lipids

membranes, steroid hormone precursor; not water soluble

cholesterol

Cholesterol Made (and degraded) in the where and must be transported through the blood to cells

liver

~1500 esterified cholesterol molecules; phospholipids

protein: apolipoproteinB-100 (binds what receptors) carries from liver to cells

LDL:low density lipoprotein

protein: apolipoprotein A-I
carries excess cholesterol to liver

HDL:high density lipoprotein

bad

LDL

good

HDL

increased heart attack risk

high LDL

decreased heart attack risk

high HDL

Receptor-mediated Endocytosis: LDLs and Cholesterol Metabolism

LDL receptors are transported to where and bound to a coated pit

plasma membrane

Receptor-mediated Endocytosis: LDLs and Cholesterol Metabolism

LDLs are taken up by Receptor-mediated Endocytosis (RME) and taken to the lysosomes, releasing what for use by the cells

cholesterol

Receptor-mediated Endocytosis: LDLs and Cholesterol Metabolism

Uptake of what from blood is critical

LDL

Receptor-mediated Endocytosis: LDLs and Cholesterol Metabolism

Familial Hypercholesterolemia (FH)
• Mutation of what Receptor

LDL

high levels in the blood promote plaque build-up in blood vessels resulting in vessel obstruction & rupture (heart attack)

LDL

A model for atherosclerotic plaque formation

1)injury to what cells

endothelial

A model for atherosclerotic plaque formation

2) attracts leukocytes and macrophages; leads to chronic what

inflammation

A model for atherosclerotic plaque formation

3)macrophages engulf LDL; cholesterol rich fatty droplets form what

foam cell

A model for atherosclerotic plaque formation

4)smooth muscle cell proliferation is stimulated

firbrous cap

Why does LDL-cholesterol accumulate in the blood?

Level of LDL receptor for apo-Bprotein is regulated by the cell’s need for what.
Cells that have sufficient what stop making the receptor.

cholesterol

For the uptake of large particles

Phagocytosis

Phagocytosis

The plasma membrane takes up a particle and pinches off to form a what

phagosome

Phagocytosis

The phagosome fuses with what and the material is digested within the phagolysosome

lysosome

Listeria monocytogenes

food-borne bacterial infection

Listeriosis

Listeria monocytogenes

How do Listeria lyse what?
-protein secretion:
-PlcA and PlcB (phospholipases)
-listeriolysin O (LLO; pore-forming)

phagosomes