9: protein folding 2 Flashcards
BiP/GRP78 interacts with what three main things?
ATF6. IRE1. PERK (which phosphorylates elF2a)
ATF6 pathway
ATF6 stops interacting with BiP, goes to Golgi, cleaved, then goes to nucleus for transcriptional upregulation of molecular chaperones, folding enzymes, ERAD
PERK pathway
upon activation will dimerize, autophosphorylate. phosphorylates elF2a which attenuates translation. also activates ATF4, transcription factor
IRE1 pathway
dimerize, autophos, splice XBP1 mRNA. xBP1 translation into transcription factor to nucleus
ER stress: flow chart to what the options are
coping response, stimulation of IRE1, PERK + ATF6 which can be adaptive to restore homeostasis, or maladaptive and cause cell death
ER stress induced apoptosis: PERK?
kinase activity of elF2a to attenuate translation, activate ATF4. ATF4 can have an adapative response but can also activate CHOP and other apoptotic proteins
under ER stress, _____ accumulate in the ER, which ______?
unfolded proteins accumualte in the ER which induces specific coping responses that may lead to survival or apoptosis
ER stress: survival pathway?
UPR (Bip: ATF6, PERK + IRE1) and ERAD (a-mannosidase, EDEM, proteasome)
ER stress: apoptosis pathway?
PERK and IRE1 = JNK, caspases, Bap, BH3 family members
calreticulin deficiency: causes?
loss of function: disrupted ER homeostasis, impaired cardiac development
calnexin deficiency
smaller size, non-aggressive, lower limb motor disorder
calnexin has no effect on?
heart or calcium homeostasis (wt and cnx knockouts look the same for heart, ca concencentrations)
calnexin: abnormality is in what?
electrophysiology: motor nerve conduction velocity impaired, sensory nerve also somewhat impaired
neuronal growth and calnexin?
neuronal growth not impaired in the absence of calnexin. calnexin deficiency has no effect on neuron number
calnexin deficient mouse: meylin?
dysmyelination: severely impaired myelin packing, very loose
calnexin deficiency: myelin proteins?
down regulated and dysfunctional ex: calnexin is a chaperone for P0, PMP22
what happens with no ERp57? no calnexin?
no ER: P0 doesn’t fold propertly (disulfide bond). no calnexin = P0 and PMP22 both not functional, non adhesive
MS: what?
chronic, progressive degenerative disorder of CNS: characterized by disseminated demyelination of nerve fibers of brain + SC
MS: disease process? affects who?
loss of myelin, disappearance of oligodendrocytes, proliferation of astrocytes. young - middle aged adults, 15 - 50yo. women more affected
MS: characterized by (3)? _____ reaction leads to?
chronic inflammation, demyelination, gliosis (scarring) in CNS. antigen-antibody reaction leads to demyelination of axons
model of MS?
experimental autoimmune encephalomyelitis EAE: concurrent inflammation of brain + SC
EAE is mediated by? induced by?
T cells. immunization with myelin proteins - animal develops cellular infiltration of myelin sheat, causes demyelination
calnexin and EAE?
calnexin deficiency: protects against EAE (and thus MS maybe) pathogenesis
