Lecture 5

Question 1

what makes phospholipids and where?

Answer 1

sER and rER in the cytosolic (inside part of the cell) lipid monolayer

Question 2

what are phospholipid translocators?

Answer 2

membrane bound enzymes that catalyze the flip flop of phospholipids from one monolayer to the other (from cytosolic side to lumen side)
-without this, new lipid bilayers could not be formed

Question 3

what’s the phospholipid exchange mechanism?

Answer 3

it’s the mechanism/protein that allows for transport of new phospholipids to other organelles’ membranes besides the ER

Question 4

Atlastin

Answer 4

GTPase

protein involved in constructing ER

Question 5

what happens with abundance and deficiency of Atlastin?

Answer 5

Abundance- increased ER membrane fusion and normal golgi is absent
deficiency- fragmentation of ER -herediary spastic (because ca) paraplegia

Question 6

Hereditary spastic paraplegia

Answer 6

leg stiffness, gait probs, stumbling dues to difficulty with hip flexion and dorciflexion of foot, retardation
caused by low Atlastin (makes ER)

Question 7

what can too much ca intracellularly do to a cell?

Answer 7

• damage membrane
• damage mitochondria leading to decreased ATP
• damage to nuclear component of cell

Question 8

Proteosomes

Answer 8

large ATP-dependent protease

located in the nucleus and cytoplasm

Question 9

What do proteases break down?

Answer 9

1) cell cycle regulating proteins
2) malformed, denatured, damaged proteins
3) antigenic proteins

Question 10

what percentage of newly formed proteins are broken down by proteosomes because they are deficient?

Answer 10

30 percent

Question 11

what happens to antigenic proteins once they are broken down by proteosomes?

Answer 11

they are presented to t cells that initiate an immune response

Question 12

What two kinds of proteosomes are there?

Answer 12

1) ubiquitin mediated- directs

2) non ubiquitin mediated

Question 13

what’s thought to inhibit proteosomes?

Answer 13

1) prion proteins

2) alzheimers plaques

Question 14

how does parkinson’s disease relate to proteosomes?

Answer 14

Parkinson’s caused by defective ubiquitination of proteins that flag the proteins for degradation by proteosomes

Question 15

How are cystic fibrosis and proteosomes related?

Answer 15

one form of CF caused by proteosomal degradation of a CFTR ABC cl channel that is slow to form but competent

Question 16

Multiple myloma and proteosomes?

Answer 16

if you inhibit proteosomes, you can help to decrease the degradation of pro-apoptotic factors that get rid of cancer cells
drug-bortezomib

Question 17

Golgi apparatus

Answer 17

• major storing and distribution center of proteins

- packages proteins into vesicles to be shipped out to other parts of the cell

Question 18

how are proteins stored in golgi?

Answer 18

based on a.a. sequence and carbohydrate moities

Question 19

How does the Golgi alter proteins?

Answer 19

1) glycosylation
2) sulfation
3) phosphorylation
4) adding of oligosaccarides (carbs) done in rER but trimmed in golgi
5) proteolytic cleavage

Question 20

anatomy of the golgi

Answer 20

3-10 sacks called cisternae that form the little flaps

Question 21

state what the movement of proteins thru the cell looks like thru the cell

Answer 21

rER to golgi to condensing vesicles to zymogens

Question 22

How is copper dealt with in the hepatic cell?

Answer 22

1) it is packaged into vesicles with the ATP7 receptor and sent out thru the bile
2) golgi in the hepatocyte has ATP7 receptor that brings copper into the golgi and attaches a protein called ceruloplasm to make ceruplasmin in the golgi and sends the ceruloplasmin out to be excreted thru the bloodstream

Question 23

wilson’s disease

Answer 23

• mutation in protein pump for the receptor for copper in the golgi of liver cells
• causes impaired secretion of copper and kaser-fleicher rings (copper deposits) in eyes and neuro probs
• decrease in cerulosplasmin because not getting copper into the golgi

Question 24

Negative golgi image

Answer 24

a pale staining area of cytoplasm seen in H and E staining

• it is NEITHER acidophilic or basophilic
• no ribosomes so pale

Question 25

Dysferin

Answer 25

- protein used to patch up microperforations in membranes of muscles cells - sent out by golgi in response to perforations - mutation in dysferin causes muscular dystrophy and myopathy

Question 26

How does the Golgi function in insulin processing?

Answer 26

1) prepro insulin made in rER and sent to golgi 2) golgi converts it to preinsulin and packages it to be shipped out with an enzyme that cleaves off the pro to give mature insulin

Question 27

proinsulinemia

Answer 27

- caused by a mutation in proinsulin that causes it to be packaged into a constitutive (continuous) secretory pathway which causes excessive excretion of proinsulin - The enzymes that are meant to cleave proinsulin and make it into insulin are still good and go down the regulated PW. - both not together so no insulin

Question 28

Cis face of golgi

Answer 28

faces the side with the incoming proteins from the rER

Question 29

trans face of golgi

Answer 29

faces where proteins are packaged and ready for secretion

Question 30

Endosomes

Answer 30

- membrane limited compartments | - organelles that sorti and identify molecules for recycling and degradation in lysosomes

Question 31

What are the four classically defined endosomal compartments | and in general how do they differ?

Answer 31

- early endosomes - recycling endosomes - multivesicular bodies - late endosomes - > they differ by having unique locations in the cytoplasm, different luminal pH, and having different molecular markers

Question 32

what's responsible for acidifying the internal environment of endosomes?

Answer 32

H+ ATPases

Question 33

what's the pH of recycling and early endosomes? How does that compare to the cytosol?

Answer 33

6.2-6.5, slightly more acidic than cytosol

Question 34

where are early and recycling endosomes located?

Answer 34

at the cells periphery

Question 35

What do recycling endosomes do?

Answer 35

recycle endosomes and glucose transport in response to insulin

Question 36

What do multivesicular bodies do, where are they located and what pH do they possess?

Answer 36

- they receive material from early endosomes and fuse with late endosomes to hand that material off - located between early and late endosomes - pH= 5.0-6.2

Question 37

why are multivesicular bodies called so?

Answer 37

because they contains lots of membranes and vessicles (from early endosomes that migrate there)

Question 38

What is the pH of late endosomes? where are the late endosomes located?

Answer 38

5.0, located near the Golgi and nucleus

Question 39

what do late endosomes do?

Answer 39

they dispose of their material (vesicles, membrane) by either fusing with lysosomes or becoming lysosomes (highest pH)

Question 40

where do most exosome like bodies come from?

Answer 40

multivesicular bodies

Question 41

How do recycling endosomes work in terms of insulin?

Answer 41

- when insulin has not binded to it's receptor on the cell surface, the recycling endosome holds the glucose transporter inside the cell - when insulin binds the receptor, it sends a signal to the recycling endosome which then sends glucose transporter up to the surface of the cell to allow for greater uptake of glucose into the cell - if prob with signal, no glucose transporter is sent to the surface of the cell

Question 42

what are the four fates of receptor-ligand complexes that have been endocytosed by endosomes?

Answer 42

1) the ligand is released intracellularly and the receptor is recycled (LDL) 2) Both ligand and receptor are recycled and sent back outta the cell (iron and it's transporter) 3) Ligand and receptor are transported across the cell and secreted via transocytosis (glandular cells (IGA) and antibodies) 4) Both ligand and receptor are degraded (FGFR3- prob= achondroplasia)

Question 43

How does Achondroplasia arise?

Answer 43

-Fibroblast growth factor and it's receptor are supposed to be used and then degraded via lysosomes BUT -in achondroplasia, theres a mutation in FGFR that prevents lysosomes from targeting it for degradation and instead it goes into the plasmalemma and is amplified causing dwarfism