Axonal Growth Lec03 Flashcards
____ changes shape at decision points
growth cone
how do neurons start (before polarization)?
round, with no obvious processes
___ defines the polarity of the neuron
the axon
where are growth cones located?
the tip of the axon
what are lamellapodium?
what do they contain?
fan shaped sheet at the tip of the axon
contain actin filaments and microtubles
what are filopodia? what do they contain?
fine processes extending out from lamellapodium
have actin filaments
___ growth cone form and disappear rapidly
filopodia
___ dictates direction of growth - in lamellipodia / filopodia
Filamentous actin (F-actin)
____ gets incorporated into F-actin at leading edge
Gobular actin (G-actin)
F-actin Binding Proteins cause ___ and ___
retrograde flow & growth cone turning (by causing depolymerixation)
attractive cue increases ___ and decreases ___
↑ polymerization/assembly, ↓ retrograde flow (goes toward the attractive cue)
functional difference ebtween MT and F-actin
MT are responsible mostly for axon elongation
f-actin dictates direction
___ make the cytoskeleton core
Microtubules (they are strong and stable)
Acetylated microtubles only in ____
axons
Tyrosinated microtubules ↑ in ____
lamellipodia
where is f actin found?
in lamellipodium and filpodia
Contact repellants include
Semaphorins and Ephrins
Contact attractants include
- peipheral ECM
- CAM
- Cadherins
___ are attractants inthe periphery, but are not well understood in the CNS?
what are examples of each?
ECM molecules
attractants - laminins, collagens, fibronectin
not well understood? repellants? – proteolgycens, glycoproteins, hyaloruonan
homolphilic binding of Cam
triggers cytoplasmic kinases of growth cone
what is Ca independent signaling? dependent
indepdent - CAM
Depdendent - caDherins
homophilic binding of cadherins triggers
intracellular signals –> actin binding &
organization
axon guidance signsla re either ___ or ___
- nondiffusable and short range
- or diffusable and long range
the contact attraction and repulsion signals are ___
nondiffusable and short range
the chemoattractants and chemorepulsive signals are
diffusable and long range
what does the binding of axon guidanc emolecules to receptors on growth cones activate?
signaling cascades that result in the reognization of growth cone cytoskeletons –> controlling the direction and rate at which the growth cone moves
attractive interactions (contact attractants and chemoattractants) promote ____
actin polymerization
repellant interactions promote ____
actin depolymerization and growth cone collapse
lamins, collagens, and fibronectins bind to ___
integrin receptors
___ has been associated with bundling (fasiculation) of groups of axons as they grow
L1 CAM
where can cadherins be found
on the suface of growth cones, growing axons, surrounding cells or targets
where are semapghorins found?
can be secreted or anchored to the cell surface
(secreted are probably attached to the cell surface or the ECM –> not really diffusable)
where do sempahorins bind to?
cell surface –> plexin family receptors
secreted –> bind neurophilins
what is the difference between the two classes of ephrins?
ephrin A has gpi linked ot surface
ephrin b is a single pass transmembrane protein
each has its own receptors on growth cone
why do temporal retina axons go to the anterior tectum?
ephrins A2 and A5 are lower in anterior
-> posterior A2 and A5 repulses the temporal axons since they have high A3
nasal retina go to the posterior tectum because
axons from the nasal retina are blind to ephrin and lack the eph receptor
so they don’t be repulsed by ephrins A2 and A5 found highly in the posterior tectum
chemorepulsion molecules include
slits
netrins if they have UNC 5 receptors
chemoattractant molecules include
netrin if they have DCC receptors
what is secreted at the embyro midline
chemorepulsants, so netrins and slits
what are slits receptors
robo
what receptors make netrin attractants
DCC
what receptors make netrin repiulsants
UNC 5
before crossing the midline ___ attracted to netrin at midline
DCC
after crossing the midline –>
cell upregualtes robo receptors, repulsion from the midline
what silences DCC signaling?
the robo that is upregulated after crossing
what does KO of netrin eliminate?
the crossing of commisural axons
why do netrin and silts have to work together?
because the cells have to cross at a very specific site in the spinal cord
also cant recross
synaptogensis in CNS
Presynaptic process (from growth cone) recognizes target cell via ____
cadherin
start of synaptgensis at the NMJ?
1. mtoor axon approaches and amkes contact with a myotube
in synaptogensis at NMJ
after mtoor axons approaches the myotube…. what happens?
nerve terminal and mytotubual diffeerentiate
nerve terminal becomes motor terminal
muscle forms post synpatic apparatus
what is the differenation of muscle induced by?
agrin –> activating MuSK –> causing clustering and increased expression of acetylcholine receptors
what does MuSK do?
causes clustering and increased expression of acetylcholine receptors
in NMJ synaptogensis, both the motor nerve and muscle make
ecm components to form a basa lamina (to stabilize the synaptic structure)
axons arising from t1 in the superior cervical ganglia form synapses on cellbodies of neurons that
project to targets in the eye
axons arising from t4 in the superior cervical ganglia form synapses on cellbodies of neurons that
project to targets in the ear
how do the correct pre and post synaptic neurons in superior cervical ganglion find eachother
they have a higher affinity than the wrong combinations
CNS synaptogensis
what recognizes the appropriate site on target cell
nascent presynaptic process via cadherin/protocadherin family
CNS synaptogensis
immediately after nascent process recognizes the target cell –>
synaptic vesicles and active zone components accumulate
CNS synaptogensis
what is recruited in the developing synapse tob ring in moilecules?
neurexin and neuroglin
where is neurorxin found?
what is its function
presynatpic
function – localizes cytoskeltal elements, vesciles, active zone proteins, and Ca channels TO PRESYNAPTIC MEMBRANE
where is neuroglin found?
what is its function?
postsynp. membrane
function – recruits NT receptors and other postsynatpic proteins
After synaptogenesis, target cells secrete
limited amounts of neurotrophic factors.
which neurons survive after synaptogensis?
those that receive enough trophic factors
Neurotrophins control the
of target cells contacted and # of synapses formed
what happens if there is NGF in check sensory ganglion?
if there is none?
yes NGF – explosion of axon extensions
no NGF – neuron death
___ respond to all growth factors
dorsal root ganglion
nodose ganglia respond best to
NT3
Sympathetic ganglia respond best to ___? and not at all to ___?
best to – NGF
not at all to BDNF
neutrophin receptors include –
Trk and p75 receptors
Trk receptors ahve a high affinity for
processed/cleaved neutrphins
p75 have a high affinity for
unprocessed enutrophin
intially, skeletal muscle and some aprsymp neurons are innveratvated by
multiple neurons
(this is eventually pruned)
with synapse elimation at the nmj, comeptition is dependent on
electricial activity in both pre and post synaptic cells
blocking electrical acitivity in either pre or post synaptic cells results in
persistence of polyneuronal innervation
axonal branching patterns are refined via
competition and synapse elimination
BDNF, NT3, NT 4/5 are all
growth factors
what is evidence for the trophic function of NGF?
no NGF –> neuronal death
excessive NGF –> survival of excess neurons
NGF are present (and produced) in target cells)
NGF
neutrophic interactions depend on
neurotrophins secreted by target cells
the neurorophin receptors present
intracellualr signaling cascade present
neutrophic interactions determine–
number of neurons, shape of neurons, patterns of neuronal connections
