Neurobiology: Unit 3

Front 1

2 families of metabotropic receptors (229)

Back 1

1. G-protein coupled receptors: activate ion channels to activate a GTP-binding protein that causes a second-messenger cascade

2. receptor tyrosine kinase: modulate ion channel activity indirectly by causing a phosphorylation reaction cascade.

Front 2

subunits of G proteins (L1)

Back 2

alpha and beta/gamma

Front 3

the cAMP cycle (L1)

Back 3

1. a transmitter binds to the extracellular portion of a beta-adrenergic receptor, causing a conformational change in the receptor.
2. The receptor can now bind the Gs protein, made up of the alpha and beta/gamma subunits attached to a GDP.
3. This causes GDP to be exchanged for GTP, which causes the dissociation of the alpha subunit from beta/gamma, which exposes the adenylyl cyclase binding site on alpha.
4. The alpha subunit binds to adenylyl cyclase, which activates it to make lots of cAMP.
5. While bound, the alpha subunit acts as a GTPase. Once GTP is converted to GDP + Pi, alpha dissociates from adenylyl cyclase (deactivating AC) and can once again bind with the beta/gamma subunits.
6. This cycle continues until the transmitter is no longer bound to the receptor.

Front 4

cAMP pathway (fig. 13.5)

Back 4

1. cAMP, produced by adenylyl cyclase, binds to 4 sites on the regulatory subunit of cAMP dependent protein kinase (PKA)
2. this causes the inactive, bound catalytic subunits to dissociate from the regulatory subunit, making the catalytic subunits active.
3. The catalytic subunits go on to phosphorylate a bunch of cellular proteins, which makes them active and causes a cellular response.

Front 5

where (with what) is PKA involved? 3 things (L1)

Back 5

1. channels
2. ion-gated channels
3. synaptic vesicle proteins

Front 6

what is the amino acid sequence that gets phosphorylated by the catalytic subunits of PKA? (L1)

Back 6

Arg-Arg-X-Ser

The serine is phosphorylated.

Front 7

diacylglycerol-inositol triphosphate pathway (fig 13.7)

Back 7

1. transmitter binds to receptor, which causes a conformational change and the activation of a G-protein
2. the alpha subunit associates with phospholipase C, activating it to cleave PIP2 into IP3 and DAG

IP3 is water soluable and diffuses through the cytoplasm to the IP3 receptor on the ER. This opens the receptor, which allows the release of Ca2+ from internal stores.

DAG is hydrophobic and remains in the membrane, where (along with membrane phospholipids), it activates protein kinase C, which is inactive unless it is brought to the membrane. PKC phosphorylates cellular proteins, causing a cellular response.

Front 8

roles of Ca2+ in the cell (L2)

Back 8

1. contraction of muscle
2. implicated in muscular dystrophy (how?)

Front 9

arachidonic acid pathway (very briefly) (fig. 13.8)

Back 9

1. transmitter causes receptor to activate a G protein. The beta/gamma subunit activates phospholipase A2 (PLA2)
2. PLA2 hydrolyzes PI in the plasma membrane, leading to release of arachidonic acid

Front 10

tyrosine kinase pathway: (L2)

what is it activated by?
what is its mechanism?

Back 10

activated by growth factors EGF, NGF, BDNF (ligands)

1. one of these growth factors bind to the extracellular domain of a tyr kinase receptor, which causes the tyrosine kinase receptors to dimerize.
2. this causes the intracellular kinase to be active: causes phosphorylation on tyrosine residues of the receptors themselves
3. this further activates the kinase, which can then phosphorylate other proteins

Front 11

where are metabotropic receptors found within the cell? (L2)

Back 11

either presynaptic, postsynaptic or around whole cell

Front 12

example of how metabotropic receptors can modulate synaptic actions--pre-synaptic (L2)

fig. 13.10

Back 12

can regulate potassium channels in the pre-synaptic cell by blocking them via phosphorylation

This causes the duration of the AP to increase, causing more synaptic release and a greater PSP.

Front 13

example of how metabotropic receptors can modulate synaptic actions--post-synaptic (L2)

fig. 13.10

Back 13

through the cAMP pathway, can keep open the ionotropic receptor allowing Na+ in, which allows a greater EPSP magnitude and AP.

also, modulation of resting voltage channels occurs, which can change threshold, space/time constants, and action potential duration

Front 14

serotonin in Aplysia (fig 13.12)

Back 14

a serotenergic interneuron makes modulatory synaptic connections on the cell body and axon of a sensory neuron that provides fast, glutamatergic connections to a motor neuron, mediating a gill-withdrawal reflex.

In this interneuron, serotonin binds to receptors and goes through the cAMP pathway, activating PKA, which phosphorylates S-type (resting) K channels, which closes them. This causes increased depolarization and a slow EPSP in sensory neurons. Due to the decreased membrane conductance (due to the closing of K channels), the voltage pulse is increased ala Ohm's law.

Front 15

relationship between core dense vesicles and metabotropic receptors (L3)

Back 15

the neuropeptides contained within the core dense vesicles activate metabotropic receptors

Front 16

what kind of molecules are released at the active zone? (L3)

Back 16

only neurotransmitters (neuropeptides aren't released at the active zone, but can be released anywhere within the neuron)

Front 17

outline the freeze fracture experiment that dealt with exocytosis (L3)

Back 17

at the NMJ

1. added voltage-gated potassium channel blocker to increase the probability of an AP.
2. used freeze-fracture technique and saw that the synaptic bouton is omega-shaped, which suggested that vesicles fuse with the membrane.

Front 18

3 steps of exocytosis (L3)

Back 18

1. fusion of synaptic vesicles with the presynaptic membrane
2. opening of fusion pore
3. complete dilation of the fusion pore and complete fusion of the vesicle with the plasma membrane

Front 19

3 theories of fusion mechanisms (L3)

Back 19

1. kiss and run
2. full fusion
3. bulk endocytosis

Front 20

kiss-and-run fusion mechanism (L3)

Back 20

Vesicle releases its contents and moves on --> NOT full fusion

dominant at low frequency stimulation

Front 21

full fusion mechanism (L3)

Back 21

dominant at high frequency stimulation, >10Hz

Front 22

synapsin protein (L3, 270)

Back 22

complexes with the cytoskeletal component of presynaptic neuron and synaptic vesicles to immobilize the vesicles

also a substrate for cAMP-dependent protein kinase and Ca2+/calmodulin dependent protein kinase

Front 23

reserve pool (L3)

Back 23

vesicles that are not mobile, tethered by synapsins

Front 24

name the 5 steps in synaptic release (L3)

Back 24

1. mobilization
2. trafficking/targeting
3. docking-priming
4. fusion
5. repair of membrane

Front 25

synaptic release: mobilization

what is it? what protein is it controlled by? how does it work?(L3, fig 14.14)

Back 25

triggers reserve vesicles to move to the active zone

controlled by synapsins (Ia, Ib, IIa, IIb)

1. Ca2+ enters the cell and eventually causes Ca2+/calmodulin-dependent kinase and PKA to phosphorylate Ia and Ib.

2. once they are phosphorylated, synapsin loses its affinity for the cytoskeleton and vesicles move into the active zone.

Front 26

synaptic release: targeting

what is it? what protein is it controlled by? how does it work? (L3, fig 14.14)

Back 26

targeting of vesicles to their release sites

controlled by proteins of the ras proto-oncogene family: Rab3a and Rab3c. Rab3a binds to GTP, and binds to synaptic vesicles. During targeting of vesicles in the active zone, Rab3a hydrolyzes its GTP to GDP (possibly makes reaction irreversible so that the vesicles must stay in the active zone).

Front 27

synaptic release: docking-priming, fusion, and repair of membrane (L3)

what complex is involved and what does it contain? how does synaptic docking work?

Back 27

the SNARES complex is involved. It contains syntaxins, SNAP25, RIM, munc13, munc18, etc.

The v-SNARE VAMP binds to the 2 t-SNARES (syntaxin and SNAP-25), promoting fusion of vesicle with membrane. Then, NSF and SNAP bind to the SNARE complex and disassemble it, using ATP. Allows for vesicle recycling.

Front 28

VSNARES, what do they do? where are they found? (L3)

Back 28

protein in vesicle membrane

bind to specific receptors in target molecules

example: VAMP (synaptobrevin)

found in nerve terminal

Front 29

effect of tetanus on VAMP

Back 29

tetanus cleaves VAMP, so that no complex forms and no synaptic release occurs.

Front 30

types of botulinum toxin and what they do (L3)

Back 30

type A: cleaves SNAP25
type B: cleaves VAMP
type C: cleaves syntaxin

essentially, prevents vesicles from docking to the membrane

Front 31

synaptotagmin (272, L3)

Back 31

inhibits exocytosis (NT release)

Front 32

what is the interaction between VAMP, syntaxin, and SNAP25 like?

Back 32

very, very stable (thus proteins NSF and SNAP must be available for recycling of vesicle)

Front 33

3 steps in the formation of the NMJ (L4)

Back 33

1. formation of selective connections between developing axons and their targets
2. differentiation of the axon's growth cones into a nerve terminal
3. differentiation of postsynaptic apparatus in the target cell.

Front 34

why was the NMJ used to study synapse formation? (L4)

Back 34

1. its large size and accessibility
2. contains a large # of receptors (ACh)
3. can use bungarotoxin to track receptor movement and to purify receptors (through specific binding)

Front 35

bungarotoxin: what is it and what do we use it for? (L4)

Back 35

binds irreversibly to ACh receptors at the NMJ

use it to track receptor movement at the NMJ and to purify receptors (through specific binding)

Front 36

list the steps in synapse formation at the NMJ (fig 55.1)

Back 36

1. myoblasts fuse to form a myotube
2. growth cone contacts the myotube
3. terminal accumulates synaptic vesicles and a basal lamina forms in the synaptic cleft
4. as the muscle matures, multiple axons converge on a single site
5. all axons but one are eliminated and the survivor matures

Front 37

myoblast (L4)

Back 37

undifferentiated muscle cell

Front 38

what event of synapse formation does ACh help shape? (L4)

Back 38

the early event (when myoblasts fuse into myotubes)

Front 39

genes controlling the formation of ACh R subunits

when do ACh R subunits form? what activity do they have?
(L4)

Back 39

ACh R form when the myotube forms and is controlled by genes encoding the subunits alpha, beta, gamma, and delta

at this point, ACh R are functional and can produce EPSPs

Front 40

ACh clustering and hot spots

what is the initial density of Ach R on the myotube?

differentiation of Ach R as NMJ matures(L4)

Back 40

at first, ACh R are distributed uniformly across the myotube at ~1000/um^2 (except that some receptors form clusters on the myotube, which are called hot spots, but as development continues, the amont of receptors is highest around the synapse (10,000/um^2), lower in the perisynaptic area (10/um^2), and lowest in the extrasynaptic area

Front 41

3 processes that effect the redistribution of ACh receptors (1092)

Back 41

1. translocation of ACh R within the membrane from non-synaptic to synaptic regions
2. transcriptional activation of the expression of genes for the ACh R subunits in the few nuclei that lie directly beneath the postsynaptic membrane
3. repression of the expression of receptor unit genes in the nuclei of nonsynaptic regions.

Front 42

experiment showing that nerves do not automatically go to hotspots in the myotube (L4)

Back 42

1. cultured frog myoblasts, added nerves
2. observed where contacts were made by labelling myotubes with fluorescent bungarotoxin

Found that synapses formed randomly, proving that the idea of predisposition was incorrect.

Front 43

so...if the idea of predisposition isn't correct, what is? (L4)

Back 43

neurites seem to contact myotubes at random. Then, new ACh R form at sites of contact.

Pre-existing clusters that are stable in the absence of the nerve disperse once the synapse forms.

Front 44

experiment that led to discovery of agrin (fig 55.6)

Back 44

1. ACh R on cultured myotubes were labeled with bungarotoxin
2. added an extracellular matrix extract and clustering of synapses occurred

They found agrin in the extracellular extract and purified it.

Front 45

structure of agrin

which type is involved in clustering? (L5)

Back 45

large heparin-sulfate proteoglycan

synthesized by motor neurons

transported down and released from nerve terminals, where it is stably associated with basal lamina.

The Z+ type is involved in clustering.

Front 46

how does agrin work? (L5)

Back 46

binds to and activates MuSK, which triggers a cascade of intracellular reactions that result in clustering.

Front 47

what is the agrin hypothesis and evidence to support it? (L5)

Back 47

agrin hypothesis: agrin is a main nerve-derived organizer of postsynaptic differentiation at the NMJ.

Evidence:
1. postsynaptic differentiation is altered in agrin mutant mice
2. introduction of agrin into muscle cell elicits formation of a complete postsynaptic apparatus
3. although myotubes and Schwann cells express agrin, Z+ agrin can cause postsynaptic differentiation.

Front 48

tell me about MuSK: what it does, its structure, etc. (L5)

Back 48

the receptor for agrin

is a transmembrane receptor localized in the postsynaptic membrane and concentrated at the NMJ

in the absence of MuSK, no clustering of receptors occurs.

yet, MuSK and agrin are not the full story --> no crosslinking occurs between the two unless muscle cell extract is added

Front 49

agrin hypothesis aside, what is the current view on the function of agrin? (L5)

Back 49

it is only involved in maintenence of clustering

Front 50

rapsyn: how was it isolated, what is known about it (L5)

Back 50

isolated by virtue of its tight association with ACh R

in absence of rapsyn, no clustering occurs

Front 51

relationship between agrin, MuSK, and rapsyn (L5, 1094)

Back 51

1. agrin released from the nerve localizes MuSK to synaptic sites and also activates MuSK.
2. MuSK then stimulates ACh receptor clustering via its kinase activity (and thus affects rapsyn?) and plays a structural role in nucleating synapse assembly.

Front 52

embryonic stages in mice as it relates to synapse formation (L5)

Back 52

1. initiation of synapse formation (synaptogenesis): E12-E16
2. maturation: E16-2 wks postnatal

Front 53

experiment with agrin, MuSK, rapsyn mouse mutants (fig. 55.6)

Back 53

1. muscles were double labeled for ACh receptors and nerves. By birth, ACh R have formed beneath each nerve terminal.
in agrin mutant Z-/-: few clusters present
in MuSK mutant: NO clustering
in rapsyn mutant: NO clustering, [but ACh R levels are higher in the synaptic area than at the ends of myotubues, reflecting the preservation of synapse-specific transcription?]

something about HB9

Front 54

what does neuregulin bind to? (L6)

Back 54

ErbB kinase receptors (tyrosine kinases)

Front 55

what are the 2 sources of neuregulin? (fig 55.7)

Back 55

can come from the motor axon or are synthesized by muscle

the kind we're concerned about are expressed by motor neurons and secreted into the synaptic cleft

Front 56

what were the circumstances under which neuregulin was isolated? (L6)

Back 56

isolated in a search for neuronal factors that stimulate ACh R synthesis by myotubes

Front 57

ErbB kinases (L6)

Back 57

neuregulin receptors

transmembrane proteins, tyrosine kinases

highly concentrated at the NMJ

Front 58

agrin causes ____ of receptors and neuregulin causes _____. (L6)

Back 58

clustering, activation

Front 59

experiment showing how agrin and neuregulin work (L6)

Back 59

1. agrin was added to myotubes and they saw clustering of receptors, but no mRNA transcripts.
2. when neuregulin was added to myotubes, they saw a lot of mRNA transcripts, but no clustering.

Thus, agrin is involved in clustering, neuregulin in activating genes.

Front 60

why can't we test the role of neuregulin in synapse formation? (L6)

Back 60

because mutant mice that lack neuregulin or ErbB die at early embryonic stages (before muscles form). Thus, their synaptic phenotypes cannot be assessed.

Front 61

experiment that knocked out Erb R (L6)

Back 61

in the absence of ErbB, the results are mixed: although there are come neuromuscular defects, at least some of the transcriptional specialization of synaptic nuclei still occurred.

Thus, 2 different conclusions:
1. axonal neuregulin might act in parallel with agrin a. (agrin-->MuSK-->Ach) b. neuregulin-->activating

2. neuregulin might act primarily as a signal from axons to Schwann cells. In its absence, Schwann cells are absent, meaning the nerve terminal is compromised, which can affect the release of agrin.

Front 62

relationship between neuregulin and Schwann cells (L6)

Back 62

when neuregulin is absent, Schwann cells are absent

Front 63

synaptic maturation in mice (L6)

Back 63

E13: receptors are diffuse in the myotube
E14: some clustering
E17: clustering of receptors
birth: many more receptors in cluster (plaque)
P5: perforation occurs
P10: differentiation of branches
P30: branches differentiated
2 years (adult): starts to degrade? synapse weakens

Front 64

tell me about plaque formation, branching, fold formation (L7)

Back 64

occurs late in embryogenesis (birth).

the borders of the cluster sharpen, the length decreases, and ACh density inreases.

after birth, the plaque becomes perforated, eventually forming a pretzel-like array of branches.

branches expand in an intercalary fashion as the muscle grows

as these changes occur, the plaque is invaginated to form folds

Front 65

when does the NMJ become functional (L7)

Back 65

before birth

neonates are completely dependent on NMJ transmission for survival

Front 66

when does synapse elimination occur

time frame
(L7)

Back 66

during early post-natal life

P0: muscle fibers innervated by multiple neurons, which are intermingled with each other.

P5: terminal segregation of neurons occurs (they begin to separate)

P10: branch withdrawal begins --> so that only one nerve innervates a muscle fiber

2 weeks: synapse elimination complete

Front 67

what is "sprouting"? (L7)

Back 67

I'm not entirely sure, but I do know that it is a sign of bad post-synaptic activity

If I had to guess, I'd say it is when synapse elimination does not happen properly and multiple axons begin growing on a myotube.

Front 68

synapse elimination (fig 55.11)

Back 68

as the NMJ develops, each myotube becomes innervated by several motor axons at a common synaptic site. After birth, all terminals but one withdraw from each site and the survivor grows.

This elimination occurs without any overall loss of axons. Axons that "lose" at some muscle fibers "win" at others.

Front 69

axotomy (L8)

Back 69

when a nerve is cut, it reinnervates slowly because the synapse forms in a new place

when it is crushed, it reinnervates quickly because the synapse reforms in the same location

causes myelin to degenerate, cell body to undergo chromatolytic reaction

Front 70

Wallerian degeneration (1108)

Back 70

when the myelin sheath (which requires axonal contact for its maintenence) becomes fragmented and is eventually enveloped, along with axonal debris by phagocytic cells.

this happens to the distal portion of the severed (pre-synaptic) neuron

Front 71

chromatolytic reaction (1108)

Back 71

the cell body swells, nucleus moves to an eccentric (ancocentric) position, and the rough ER becomes fragmented. Metabolic changes also occur.

Changes are reversible if regeneration is successful; otherwise, the cell may die.

Front 72

how does axotomy affect the input cell?

also, chain reactions in pre- and post- syn cells(1108)

Back 72

synaptic stripping may occur

antero- and retrograde degeneration can occur: a denervated neuron that becomes severly atrophic can fail to activate its target, which then becomes atrophic as well. Same with synaptic stripping.

Front 73

synaptic stripping (1108)

Back 73

when synaptic terminals withdraw from the neuronal cell bodies of chromatolytic neurons and are replaced by the processes of glial cells.

depresses synaptic function and can impair recovery of function

Front 74

reactive astrocyes (1109)

Back 74

glial cells in the CNS that participate in synaptic stripping in response to Wallerian degeneration and contribute to the formation of a glial scar

immune cells can also be recruited to form a scar

Front 75

proximal stump

distal stump
(1109)

Back 75

proximal stump is the part of the severed neuron that contains the cell body

distal stump is the part that is separated from the cell body

Front 76

axonal sprouts, and mechanism (1109)

Back 76

Axonal sprouts grow from the proximal stump, enter the distal stump, and grow toward the nerve's end-organs.

chemotropic factors secreted by Schwann cells attract axons to the distal stump, adhesive molecules within the distal stump promote axon growth along cell membranes, and inhibitory molecules in the perineurum prevent the regenerating axons from going astray.

Front 77

compare regeneration in the PNS and CNS (1110)

Back 77

All three branches of the PNS can regenerate (though sometimes fine motor skills are not as good as before). Regeneration is poor without laminin (protein in the basal lamina), which is plentiful in PNS, but not in CNS.

In the CNS, little regeneration can occur

Front 78

CNS regeneration and inhibitory factors (1111)

Back 78

was proposed that both the PNS and CNS contain a large amount of growth-promoting elements (laminins, tropic molecules), but the CNS contained inhibitory factors, like central myelin. Myelin 35 inhibits outgrowth of neurons in CNS.

Front 79

CNS regeneration and secondary changes in cell environment (1111)

Back 79

A number of events are prominent following brain injury: astrocyte proliferation, activation of microglia, scar formation, inflammation, invasion by immune cells. These changes may render an otherwise permissible environment inhospitable.

Front 80

experiment, Viktor Hamburger (L9)

Back 80

showed that the number of sensory neurons in dorsal root ganglion of amphibian embryos was increased by transplantation of an additional limb bud into the target field

thus, the target influences proliferation and differentiation of sensory neurons.

Front 81

experiment with chick embryos, muscle buds (L9, fig 53.11)

Back 81

she removed a developing limb bud and noticed that while motor neurons were generated at normal levels, later in development, few motor neurons remain on the side of the spinal cord on the side of the missing limb (# of motor neurons is 50% as much).

When she transplanted an extra limb bud onto the embryo, she saw that it reduces the extent of naturally occuring cell death so that 75% of motor neurons survive on the side that has 2 limb buds.

When she blocked muscle activity by curare, it reduces extent of motor neuron death so that 75% of neurons survive on both sides.

thus: size and muscle target are critical for survival of spinal motor neurons. Led to the neurotropic factor hypothesis.

Front 82

neurotrophic factor hypthothesis (L9)

Back 82

neurotropic factors are released by the source (muscle, for instance). Those neurons that take up the NF live and those that don't, die.

another perspective on synapse elimination

Front 83

the first and second neurotropic factors introduced

and others(L9)

Back 83

first: nerve growth factor (NGF)
second: BDNF

then, neurotrophin 3, 4/5

Front 84

explain why the chick embryos treated with curare had less cell death than normal (L9)

Back 84

survival of motor neurons depends on muscle activity, so in the absence of post-synaptic activity (by using curare, for example), cell death is prevented and survival of motor neurons is enhanced.

electrical activity in neurons themselves is required for appropriate response to NFs.

Front 85

explain how activity can control production of NFs (L9, 1055)

Back 85

activity in the target cell could inhibit production of NF. Because the supply of NF is thought to be limited, any reduction in the supply would lead to a greater degree of neuronal death.

And the thing about the chick embryos: if there is no electrical activity (due to curare), neurons cannot respond correctly to NFs.

Front 86

2 classes of neurotrophic factors (L9)

Back 86

1. Trks (tropomyosin receptor kinases): TrkA, B, C. NFG binds preferably to trkA. BDNF and neurotroph 4/5 bind to trkB. Neurotroph 3 binds to trkC, but specificity is not absolute)

2. p75: all neurotrophins bind to this, but affinity for it is very low

Front 87

experiment with sympathetic neurons in the presence of NGF (L9)

Back 87

when NGF was added to sympathetic neurons, the neuron grew like crazy. When it was not added, no growth occured.

Front 88

experiment with pyramidal neurons with BDNF and APV (L9)

Back 88

when BDNF was added to pyramidal neurons, the neuron grew like crazy. When BDNF + APV were added, no growth occured, showing that NMDA R are involved in neurogenesis somehow.

Front 89

trk receptors: structure (L10)

Back 89

transmembrane glycoproteins

tyrosine kinases with extracellular ligand binding domain containing multiple repeats, leucine-rich motifs, 2 cysteine clusters, 2 immunoglobin-like domains and a single transmembrane domain.

each trk receptor binds a ligand through a specific sequence.

Front 90

what does activation of trk receptors depend upon? (L10)

Back 90

dimerization of receptors, a process initiated by the binding of the ligand. This leads to the activation of different signaling pathways through recruitment of various adaptor molecules.

Front 91

what happens to the tyrosine residues on the trk? (L10)

Back 91

they become phosphorylated and recruit PLC-gamma, which catalyzes the cleavage of the substrate of PIP2--> IP3 and DAG, leading to release of Ca2+ from internal stores.

Front 92

NGF (L10)

BDNF

NT4/5

NT3

Back 92

NGF: a NF that controls sensory neurons of the dorsal root ganglia

BDNF: control mechanoreceptors on Merkel cells

NT4/5: control deep-hair cell

NT3: control many dorsal root ganglia neurons, early development.

Front 93

apoptosis: why is it important? (L10)

Back 93

an important mechanism involved in development and homeostasis in adult tissue.

important because apoptosis can remove infected, transformed, or damaged cells

Front 94

3 things that characterize apoptosis (L10)

Back 94

1. fragmentation of the cell into membrane-bound bodies
2. nuclear and cytoplasmic condensation
3. endolytic cleavage of DNA into small oligo fragments. The cells on these fragments are then phagocytosed by macrophages.

Front 95

3 examples of how apoptosis is needed for proper development (L10)

Back 95

1. resorption of the tadpole tail at the time of metamorphesis.
2. formation of fingers and toes in fetus
3. synapse elimination

Front 96

3 things than can trigger apoptosis (L10)

Back 96

1. cell surface receptors
2. signal rising within the cell
3. dangerous reactive oxygen species like H2O2 or hydroxy radicals

Front 97

apoptosis proteins in c. elegans and vertebrates

relation to NFs(L10)

Back 97

ced9 protein acts upstream of and inhibits activity of ced4, which is responsible for activation of ced3. activation of ced3 results in the cleavage of protein substrates and results in cell death.

In vertebrates, BCl2 (ced9) inhibits Apaf-1 (ced4) which activates caspase (ced3) and leads to cell death.

If NFs bind, it blocks Apaf-1, which means that cells survive