Membranes III

Question 1

the first ___-____ aa translated will determine if the protein continues to be translated in the cytoplasm or contains the _____ ____ that will cause the ribosome/nascent protein complex to relocate to the ER to finish translation of the protein

Answer 1

the first 20-25 aa will determine if the protein continues or contains the Signal Sequence

Question 2

possibles fates of proteins that are translated completely on cytoplasmic ribosomes (4)

Answer 2

(1) cytoplasm
(2) nucleus
(3) mitochondria
(4) peroxisomes

Question 3

possible fates of proteins that finish translation in the ER (5)

Answer 3

(1) plasma membrane
(2) ER
(3) golgi
(4) lysosomes
(5) secretion

Question 4

mucopolysaccharidoses is an

Answer 4

LSD

Question 5

why is I-Cell disease important?

Answer 5

it revealed the mannose-6-phosphate address label for lysosomal enzymes, opened up the whole field of LSDs, and taught us how lysosomes and several other organelles are made

Question 6

In I Cell disease, the defect is in the ________________ enzyme that _________ the 6-position on specific ______ residues

Answer 6

the defect is in the phosphotransferase enzyme that phosphorylates the 6-position on specific mannose residues

Question 7

targeting signal for all lysosomal enzymes

Answer 7

6-position on mannose residue

Question 8

lysosomal enzymes are secreted from the cell, leaving lysosomes as an empty bag devoid of degradation enzymes

Answer 8

I-Cell

Question 9

consequence of the I-Cell defect

Answer 9

lysosomes fill up with all the substrates they usually degrade and appear under the microscope as large, dark inclusion bodies

Question 10

Protein targeting sequence 1

Answer 10

S-K-L is the tripeptide sequence that targets proteins to the peroxisome

Question 11

Protein targeting sequence 2

Answer 11

short (typically 5-6) basic aa sequences are the NLS

Question 12

Protein targeting sequence 3

Answer 12

mannose-6-phosphate targets proteins to the lysosome (its the only non-peptide address label)

Question 13

Protein targeting sequence 4

Answer 13

a longish (about 75 aa) sequence near the N-terminal end of the protein directs proteins to mitochondria

Question 14

Protein targeting sequence 5

Answer 14

K-D-E-L is the tetrapeptide sequence targeting proteins to the ER (it is actually an ER retention signal)

Question 15

peroxisome targeting disease

Answer 15

Neonatal adrenoleukodystrophy (NADL) and Zellweger syndrome

Question 16

nuclear targeting disease

Answer 16

Huntington’s

Question 17

invagination

Answer 17

RME- receptor mediated endocytosis

Question 18

clathirin is on the ____ side for RME

Answer 18

cytoplasm

Question 19

clathirin coated vesicles are called

Answer 19

endosomes

Question 20

homozygous condition on the dark side of RME leading to high LDL

Answer 20

familial hypercholesterolemia

Question 21

Infleunza and rabies virus gets into the cell by

Answer 21

RME

Question 22

Many viruses use RME to get inside the cell, then fuse with the _________

Answer 22

endosomes

Question 23

true or false: clathirin help concentration of the ligands by sending a signal

Answer 23

true

Question 24

true or false: all protein synthesis occur in the cytoplasm

Answer 24

true

Question 25

SKL

Answer 25

presoxisomes

Question 26

KDEL

Answer 26

ER "keep in the ER"

Question 27

long, N-terminal aa sequence

Answer 27

mitochondria

Question 28

short, basic aa sequence

Answer 28

nucleus

Question 29

important signal for dilated mycocardiopathy

Answer 29

plasma membrane

Question 30

recognize miss-folded proteins

Answer 30

chaperones

Question 31

inducible by conditions that cause unfolding of newly synthesized proteins

Answer 31

Heat shock proteins

Question 32

transmembrane protein in the ER membrane needs a

Answer 32

stop-transfer sequence

Question 33

stacks of cisterne

Answer 33

golgi

Question 34

cis golgi

Answer 34

close to the nucleus

Question 35

trans golgi

Answer 35

close to the plasma membrane

Question 36

phosphorylation of proteins destined to be _______ _______occurs at the ______ golgi

Answer 36

phosphorylation of proteins destined to be lysosomal enzymes occurs at the cis golgi

Question 37

processing and sorting occurs at the ______ golgi

Answer 37

trans

Question 38

lysosomes are full with ______ enzymes that work best at the ____ ph achieved by the _____ pump

Answer 38

lysosomes are full with degradative enzymes that work best at the low ph achieved by the H+ pump

Question 39

low ph in an endosome allows for

Answer 39

a vesicle to be pinched off containing the receptor to be recycled

Question 40

deficiency in iduronate 2-sulfatase

Answer 40

MPS dx--> hunter's disease

Question 41

caused by a defective phosphototransferase, such that lysosomal enzymes do not get properly tagged

Answer 41

I-Cell

Question 42

where do the proteins destined for the lysosome acquire a phosphate group on the 6-positon mannose

Answer 42

Cis golgi body

Question 43

if the first 20-25 amino acids on a proteins N-terminal are not hydrophobic, the completed protein's default destination is the

Answer 43

cytoplasm

Question 44

a protein will be transported to the ____ if it has a hydrophobic signal peptide

Answer 44

ER

Question 45

4 fates of protein that finishes translation in cytoplasms

Answer 45

1. Nulceus 2. Mitochondria 3. Peroxisomes 4. Cytoplasm

Question 46

5. fates of protein that finished translation in membrane-bound ribosome

Answer 46

1. E.R. 2. Plasma membrane 3. Secretory Vesicles 4. Lysosomes 5. Golgi

Question 47

Nucelar localization signal (sequence)

Answer 47

Lys-Lys-Lys-Arg-Lys

Question 48

Diseases of peroxisomal targeting (2)

Answer 48

1. Zweller Syndrome | 2. NALD

Question 49

Golgi membrane between cis and trans

Answer 49

Medial region

Question 50

3 fates of proteins that go through golgi

Answer 50

1. Lysosome 2. Plasma membrane 3. Secretory vesicle

Question 51

pH of lysosomes

Answer 51

5

Question 52

Low lysosomal pH is achieved by

Answer 52

H+ pump

Question 53

Lysosome deficiencies are due to a single _______

Answer 53

Lysosome deficiencies are due to a single enzyme deficiency

Question 54

Targeting signal of nucleus

Answer 54

Short basic aa sequence

Question 55

Pathology of problem with targeting signal of nucleus

Answer 55

Huntington

Question 56

Targeting signal of peroxisome

Answer 56

SKL tripeptide

Question 57

Targeting signal of mitochondria

Answer 57

70-80 aa sequence near N-terminus

Question 58

Problem with targeting signal of mitochondria

Answer 58

mitochondriopathies

Question 59

Targeting signal of lysosome

Answer 59

Mannose-6-phosphate

Question 60

Problem with targeting signal of lysosome

Answer 60

I-cell disease

Question 61

Targeting signal of ER

Answer 61

KDEL tetrapeptide

Question 62

Problem with targeting signal of ER

Answer 62

Dilated cardiomyopathies

Question 63

Sphingolipid metabolism defect; first LSD successfully treated with enzyme replacement therapy

Answer 63

Fabry

Question 64

Sphingolipid metabolism defect; also successfully treated with enzyme replacement therapy

Answer 64

Gaucher

Question 65

Sphingolipid and glycosaminoglycan (GAG) metabolism defect prevalent in Ashkenazi Jews

Answer 65

Tay-Sachs

Question 66

Defect in one of the several enzymes needed to break down GAGs (aka mucopolysaccharides); several are now treated with enzyme replacement or enzyme enhancement therapies

Answer 66

Mucopolysaccharidoses (MPS)

Question 67

Defect in the phosphoryltransferase that puts a phosphate group on the 6-position of specific mannose residues; no lysosomal enzymes get to lysosomes, thus all substrates constipate the lysosome; rare disease that revealed mechanisms for LSD pathogenesis and lysosomal/organellar biogenesis

Answer 67

I-Cell Disease

Question 68

Key Point: While each individual LSD has an incidence of 1 in 100,000 or less, there are so many of them that the overall likelihood of an individual having an LSD is about 1 in _____

Answer 68

3000