Ch 13 Pt 2

Question 1

Lysosomes

Answer 1

Membrane-enclosed organelles filled with soluble hydrolytic enzymes that digest macromolecules

are more acidic than cytosol (because allows for optimal faction of acid hydrolases)

Question 2

sugar modified protines on the membrane in the lysosome

Answer 2

are a barrier to precent digestion of protines

Question 3

What happens of hydrolases leak out of the lysosome?

Answer 3

They will not be as active because of the pH difference.
Is a protection mechanism

Question 4

Lysosome Maturation

Answer 4

Late endosomes - chop up and (begin) digest debree (contain material from PM and new hydrolases)-> endolysosome mature into lysosomes once hydrolases complete digestion

Question 5

Delivery to lysosome

Answer 5

1. Nutrients - receptor mediated - endocytosis
2. Captures fluids
3. Engulf microbe, phagocytosis
4. autophagy - not begin at cell surface, begins at cytosol

Question 6

Autophagy

Important in ___

can digest ___

Answer 6

Self Eating

Important in growth and development (helps restructure differentiating cells)
gets rid of organelles not functioning well

Can digest large objects (proteasome can’t handle)

Question 7

Selective vs Nonselective Autophagy

Answer 7

Selective - initiated by signal - induce fusing of vesicles (capture cytosol and organelles) - forms a autophagosome - fuse with lysosome - degradation

Non selective - new born babies and in starvation conditions. Capture whatever it can be used for nutrients

Question 8

How are lysosomal hydrolases recognized and selected in the Trans Golgi?

Answer 8

Unique Marker: Mannose-6-phosphate (M6P) - becomes tag - recognized by M6P receptor

(N linked oligosaccharide - added in ER)

Question 9

Transport of lysosomal hydrolase to endosome

Answer 9

Happens in Golgi.
With Tag - recognize for packing into clathrin coated vesicles - sent to the lysosome
Fuse with early endosome - disassociates (receptor and protein) promoted by lower pH - release hydrolase.
Receptor is brought back with retromer coat.

Question 10

I-cell disease

Answer 10

Inclusion-cell disease
mutation in enzyme responsible for adding M6P tag. (defect in GlcNAc phosphotransferase)

Almost all hydrolytic enzymes are missing from lysosomes of many cell types. Undigested material accumulates in lysosomes, formation of large inclusions in cells.

Hydrolases are secreted (found in blood)

organ falure (6-7 years lifespan)

Question 11

Endocytosis

Answer 11

-cells take up PM components, fluid, solutes, macromolecules

Material ingested is enclosed by small portion of PM, which first invaginates and then pinches off, forming an endocytic vesicle

Cell regulates its membrane composition in response to changing extracellular conditions

Question 12

From the Plasma Membrane to Lysosome

Answer 12

Most endocytic vesicles fuse with receiving compartment (early endosome), where internalized cargo is sorted.

Some returned to PM (recycling endosome) and some designated for degradation (late endosome).

Question 13

Early vs late endosome

Answer 13

Early:
- Has tublar domains, can recycle
- Recieves endocytoic vesicles
- Vacular domain
- Branches - lost in Late
- from golgi to early - inactive enzymes (because still recycling)
- closer to plasma membrane

Late:
- more intraluminal vesicles
- no more recyling
- inc. digestion
- destin for degredation
- more actic, (enzymes that degrade are more active)

Question 14

Golgi and early endosome

Answer 14

gets inactive enzymes (hydrolases) from golgi (zymogens)

Question 15

in multivescular body

Answer 15

change in rabs and snares so that late can fuse with lysosome
invagenate - bring into (membrane protein) endosome for digestion

Question 16

Ealy endosome
location
Presence of Vacuolar Portions
Presence of Tubular Portions
Site of Recycling
Activity of hydrolases
Presence of intralumenal vesicles
Site of Digestion
What membrane fuses with endosome?

Answer 16

location - close to PM
Presence of Vacuolar Portions - Yes
Presence of Tubular Portions - Yes
Site of Recycling - Yes
Activity of hydrolases - very low
Presence of intralumenal vesicles - No
Site of Digestion - No
What membrane fuses with endosome? - fuses with incoming endocytic vesicles

Question 17

Late endosome
location
Presence of Vacuolar Portions
Presence of Tubular Portions
Site of Recycling
Activity of hydrolases
Presence of intralumenal vesicles
Site of Digestion
What membrane fuses with endosome?

Answer 17

location - interior of cell
Presence of Vacuolar Portions - Yes
Presence of Tubular Portions - No
Site of Recycling - No
Activity of hydrolases - Very active - very acetic
Presence of intralumenal vesicles - Yes
Site of Digestion - Yes (Destin for degradation)
What membrane fuses with endosome? lysosome (from endolysosome)

Question 18

Why respond to insulin so fast

Answer 18

recycling endosome
strage ceter for glucose transporters, moblization to PM, uptake of glucose

Question 19

Receptor Mediated Endocytosis

Answer 19

taking up “SPECIFIC” macromolecules from extracellular fluid
Macromolecules bind to specific receptors, which accumulate in coated pits
Example: Import cholesterol in mammalian cells - LDL has specific rector forms coated vesicel

Question 20

Receptor Mediated Endocytosis of LDL

Answer 20

LDL binds to R - clatorin coated - uncoat - fuse with early endosme very acitic vs cytosol, dissasocation of R from LDL - late - fuse with lysosme - degrade LDL “package” - release of cholestorl

Question 21

Exocytosis: From the trans Golgi to the Cell Exterior

Answer 21

Transport vesicles destined for PM leave Trans Golgi network in steady stream as irregularly shaped tubules

Membrane proteins and lipids inside vesicles, provide new components for PM. Soluble proteins are secreted to extracellular space

Fusion of the vesicles with plasma membrane: called Exocytosis

Question 22

Pathways of protein sorting in trans Golgi network

Answer 22

1. gets hydrolases to lysosome (M6P R)
   3.. defult pathway - make changes - bring in components un unrgulated way - gets enxymes without a tage - to PM
2. Regulated - singal relase of secretoy proteins (ex. NT)

Question 23

Secretory proteins become highly concentrated in secretory vesicles because

Answer 23

Clathrin coated vesicles retrieve membrane and luminal content back to Golgi

Secretory proteins aggregate in acidic environment

Vesicles fuse

Question 24

Secretory vesicel and protelitic processing

Answer 24

hormaones are very short - hard to co translation so made as large - also need location signal

differnt hormones are active where they function (protect cell from unwanted degredation)

Question 25

Synaptic vesicles (specialized secretory vesicles)

Answer 25

Docking of vesicle at presynaptic plasma membrane Priming step: SNAREs partly paired, helices not fully wound. Complexins frexe snare complex, prevents fustion ot membrane so when singal comes it is ready Fustion: Action potential arrives at nerve terminal, influx of Calcium ions through voltage-gated Ca2+ channels Rise in calcium: triggers binding of Synaptotagmin (contains calcium binding domains) to phospholipids and SNAREs, displacing complexins. Fusion pore opens and neurotransmitters are released

Question 26

The botulinum toxin causes

Answer 26

muscle paralysis prevents the release of acetylcholine from presynaptic axon of motor neurons. has heavy and light chain heacy chanin txin binds to R to be endocytosed, once in vesicle ligh chai relseased and dissables/cleaves snares so can not longer assemble

Question 27

NPC

Answer 27

rare autosomal recessive NPC1 - 75% of cases fatail, lipid sorage disease diagosed with Filipin staining: Filipin is a fluorescent antibiotic that binds to cholesterol NPC1 transmembrane glycoprotein: Localizes to late endosomes and lysosomes NPC1 is essential for transporting cholesterol and other lipids out of lysosomes, but little is known about the mechanisms that control its cellular abundance and localization. Cholesterol binds to NPC1 is exported from late endosomes/ lysosomes to the ER and plasma membrane by an unknown mechanism.

Question 28

NPC1 symptoms

Answer 28

Early childhood usually normal (jaundice may occur at birth) Behavior problems (school age), The child will progressively develop loss of intellectual function, clumsiness, and difficulty with upward and downward eye movements, difficulties with speech, swallowing spleen or liver enlargement (may occur) Psychiatric disturbances may develop Sudden loss of muscle strength Fatal, neurodegenerative disease: Death from complications of the disease usually occurs in the teenage years or early adulthood. Loss of myelin sheath slows signal transduction

Question 29

NPC1 treatment

Answer 29

Cyclodextrin are molecules comprising starch and sugar rings that may be able to help brain cells discharge (efflux) cholesterol (cholesterol lowering drug).