9: protein folding 2

Question 1

BiP/GRP78 interacts with what three main things?

Answer 1

ATF6. IRE1. PERK (which phosphorylates elF2a)

Question 2

ATF6 pathway

Answer 2

ATF6 stops interacting with BiP, goes to Golgi, cleaved, then goes to nucleus for transcriptional upregulation of molecular chaperones, folding enzymes, ERAD

Question 3

PERK pathway

Answer 3

upon activation will dimerize, autophosphorylate. phosphorylates elF2a which attenuates translation. also activates ATF4, transcription factor

Question 4

IRE1 pathway

Answer 4

dimerize, autophos, splice XBP1 mRNA. xBP1 translation into transcription factor to nucleus

Question 5

ER stress: flow chart to what the options are

Answer 5

coping response, stimulation of IRE1, PERK + ATF6 which can be adaptive to restore homeostasis, or maladaptive and cause cell death

Question 6

ER stress induced apoptosis: PERK?

Answer 6

kinase activity of elF2a to attenuate translation, activate ATF4. ATF4 can have an adapative response but can also activate CHOP and other apoptotic proteins

Question 7

under ER stress, _____ accumulate in the ER, which ______?

Answer 7

unfolded proteins accumualte in the ER which induces specific coping responses that may lead to survival or apoptosis

Question 8

ER stress: survival pathway?

Answer 8

UPR (Bip: ATF6, PERK + IRE1) and ERAD (a-mannosidase, EDEM, proteasome)

Question 9

ER stress: apoptosis pathway?

Answer 9

PERK and IRE1 = JNK, caspases, Bap, BH3 family members

Question 10

calreticulin deficiency: causes?

Answer 10

loss of function: disrupted ER homeostasis, impaired cardiac development

Question 11

calnexin deficiency

Answer 11

smaller size, non-aggressive, lower limb motor disorder

Question 12

calnexin has no effect on?

Answer 12

heart or calcium homeostasis (wt and cnx knockouts look the same for heart, ca concencentrations)

Question 13

calnexin: abnormality is in what?

Answer 13

electrophysiology: motor nerve conduction velocity impaired, sensory nerve also somewhat impaired

Question 14

neuronal growth and calnexin?

Answer 14

neuronal growth not impaired in the absence of calnexin. calnexin deficiency has no effect on neuron number

Question 15

calnexin deficient mouse: meylin?

Answer 15

dysmyelination: severely impaired myelin packing, very loose

Question 16

calnexin deficiency: myelin proteins?

Answer 16

down regulated and dysfunctional ex: calnexin is a chaperone for P0, PMP22

Question 17

what happens with no ERp57? no calnexin?

Answer 17

no ER: P0 doesn’t fold propertly (disulfide bond). no calnexin = P0 and PMP22 both not functional, non adhesive

Question 18

MS: what?

Answer 18

chronic, progressive degenerative disorder of CNS: characterized by disseminated demyelination of nerve fibers of brain + SC

Question 19

MS: disease process? affects who?

Answer 19

loss of myelin, disappearance of oligodendrocytes, proliferation of astrocytes. young - middle aged adults, 15 - 50yo. women more affected

Question 20

MS: characterized by (3)? _____ reaction leads to?

Answer 20

chronic inflammation, demyelination, gliosis (scarring) in CNS. antigen-antibody reaction leads to demyelination of axons

Question 21

model of MS?

Answer 21

experimental autoimmune encephalomyelitis EAE: concurrent inflammation of brain + SC

Question 22

EAE is mediated by? induced by?

Answer 22

T cells. immunization with myelin proteins - animal develops cellular infiltration of myelin sheat, causes demyelination

Question 23

calnexin and EAE?

Answer 23

calnexin deficiency: protects against EAE (and thus MS maybe) pathogenesis