Functional Polarity Flashcards
what does a simple polarised cell look like?
a standard cell with differing apical and basolateral surfaces?
what’s a highly polarized cell?
neuron
what 3 components make up cell cytoskeleton?
microtubules
microfilaments
intermediate fibres
what are microtubules made of?
tubulin
in which direction do microtubules grow?
radially- from nucleus outwards
what are microfilaments made of?
actin
what’s the order of transmission of a neuron- starting from synapse?
synapse –> dendrite –> cell body–> axon–> synapse
what does a developing neuron look like?
cell body with branching neurites and a growth cone and end with filopedia coming out
what happens during stage 1 (day 0) of neuron development?
plated neurons make lamellopedia
what happens during stage 2 (day 0.5) of neuron development?
neurons extend in several places- short processes of equal length
what happens during stage 3 (day 1) of neuron development?
one process begins growing rapidly and acquires axonal features
what happens during stage 4 (day 4) of neuron development?
remaining processes grow slowly and acquire dendrite characteristics
what happens during stage 5 (days 7-10) of neuron development?
neurons are fully polarized and synapses begin to form
what drives neuronal polarity?
cytoskeleton
which of the 3 cytoskeleton components have polarity?
microtubules
microfilaments
describe the axon in terms of cytoskeleton
all microtubules orientated with + ends outwards and associate with specific binding proteins to become stabilized polymers
describe the dendrites in terms of cytoskeleton
start with being all +end microtubules, but later become mixed with + and - ends facing both directions
how long are microtubules?
25nm
what, structurally are microtubules?
hollow tubes
what binds microtubules?
GTP
how long are intermediate filaments?
10 nm
what, structurally are intermediate filaments like?
rope- like
how long are microfilaments?
7nm
what, structure do microfilaments have?
helical
what binds microfilaments?
actin
how do microtubules form?
a and B tubulin are globular proteins
dimerise to form a aB heterodimer
polymerise to form protofilament chain
lateral interactions between a to a and B to B chains form a cylindrical microtubule structure- mature
what end is exposed in a-tubulin?
-
what end is exposed in B-tubulin?
+ (fast growing)
what are the subunits of tubulin?
enzymes that catalyyze GTP to GDP
how do subunits add and leave tubulin?
T-form recruited at +end
D-form shed from minus end (as - end is less stable)
what’s it called when a tubulin polymer is at constant length?
treadmilling
what’s it called when tubulin GTP hydrolysis is faster that subunit addition?
dynamic instability (shrink)
what influence the rate at which microtubules grow?
MAPs - bind +end
what are the subunits in neuronal intermediate fibres?
neurofilaments
what are neurofilaments abundant in?
myelinated axon
what are the 3 types of NF filament?
light
medium
heavy
how do intermediate fibres form?
the neurofilaments form dimers, then tetramers then 8 tetramers associate to form rope-like filaments
do neurofilaments have polarity?
no
what do tail domains of H and M neurofilaments do?
radiate outwards due to extensive -ve charges
what forms the bulk of the axon?
neurofilaments
what in the axon do neurofilaments dictate?
the width - as they are added along the width as well as the ends
by dictating the width of the axons, what do neurofilaments therefore do?
dictate the speed of nerve conduction
structurally, what do intermediate filaments provide the neuron with?
tensile strength
why are neurofilaments spaced out evenly through the axon?
mutual -ve charge repulsion
what’s similar between actin and tubulin?
made up of a globular peptide
binding site for substrate
polarity - undergo treadmilling
what’s different between actin and tubulin?
actin uses ATP, tubulin GTP
actin in a right- handed helix
where is actin particularly dense?
below the cell membrane
what do integrins do?
link actin in cytoskeleton with extracelluar matrix
How do scientists study axonal protein transport?
cutting/tying an axon at a certain point. take different segments and see where protein accumulates - find direction of travel
is axonal transport passive or active?
active
is there one or many shapes of dendrite?
many
what are the structural characteristics of dendrites? (5)
tapered, branched, emerge from soma, continuous cytoplasm with soma
zooming on dendritic region what are the strcutures?
dendritic region > branchlet > spine cluster > spine
how are dendrite spines imaged in vitro?
mouse kill mouse remove brain microdissect desired brain region cut 200 micrometre sections transfect/ GFP tags image
what are the different morphologies of dendritic spines going from immature to mature?
filopodium thin stubby mushroom cup
what changes spines?
age and experience
what’s happening to spines during early post-natal life?
spinogenesis- new spines forming
what’s happening to spines during adolescence?
lots of new spines forming
what’s happening to spines during early adulthood?
mass spine pruning of unused spines
what’s happening to spines during adulthood?
maintenance, some pruned some new
give examples of 2 disorders with decreased spines
down syndrome
epilepsy
what’s been found about spines from honey bees?
older, more experienced foraging bees have more spines about younger/less experienced ones and loads more than nurses (who stay in the hive)
what do dendritic spines serve at?
calcium concentrating comapartments- for signals
what’s the name of the firs segment of axon coming out of soma?
Axon Initial Segment (AIS)
what does the AIS act as?
a physical diffusion barrier between somatodendritic and axonal compartment
is the AIS often or rarely innervated?
rarely
what neurotransmitters do the few axons that synapse onto the AIS use?
GABA- inhibitory- shuts down inputs
what’s the axon rich in?
actin and ankynin G
what is ankynin G used for?
localising and immobilising sodium channels
in what 2 ways are Na+ channels compartmentalised at AIS?
Direct transport- when they are inserted into the AIS membrane
or
Elimination/ retention- they are produced evenly spread throughout neuron and removed everywhere other than AIS by endocytosis
describe axon structure?
long, untapered, cylindrical, 1 micrometre thick, can have collateral branches at 90 degrees, can be myelinated
are axons often or rarely innervated?
rarely
what myelinates axons in PNS?
schwann cells
what myelinates axons in CNS?
oligodendrocytes
what’s non decremental energy?
no energy lost
are axons made up of one long tubule or many little ones?
many little ones overlapping in parallel
in a axon, which end of microtubules are pointing outwards?
+ ends
what’s fast axonal transport?
membrane bound protein movement at 200-400 mm a day
what’s slow axonal transport?
membrane bound protein movement at 0.1-200mm a day
what’s anterograde transport?
from soma to axon end/ synapse
what’s reterograde transport?
from axon end to soma
what does fast anterograde transport carry (2)
- membranous organelles e.g. mitochondria
- vesicles carrying neurotransmitters and enzymes for activation
what is fast anterograde transport mediated by?
kinesins
what are kinesins?
specialised microtubule binding proteins
how many members of the kinesin family?
14
what’s the structure of kinesin?
2 globular motor domains (ATP binding sequence and microtubule binding sequence)
filamentous stalk
cargo-binding site in tail region - for vessicles/ membranous organelles
how do kinesins move?
2 globular heads motor head binds microtubule ATP associates with molecule ATP hydrolysis causes a conformational change in kinesin , new association with molecule is formed -1 step
how are kinesin families catergorized?
by the position of their motor domain on the microtubule
what are the 3 families of kinesin?
N- kinesin- bind NH- terminal
M-kinesin- bind middle of microtubule
C- kinesin- bind -COOH end (- end)
what drives microfilament movement?
myosin
what’s faster myosin on microfilament or kinesin on microtubule?
kinesin on microtubule
what is carried by fast retrograde axonal transport?
- endosomes
- mitochondria
etc. to soma for degradation by lysosomes and recycling
what takes advantage of fast anterograde axonal transport?
toxins
viruses e.g. HIV and tetanus
which protein performs fast retrograde axonal transport?
dynein - along microtubule tracks
is dynein large or small?
large
what end of microtubule does dynein bind?
- end
what’s required for dynein binding to microtubule?
dynactin association binding to MT
what allowd dynein movement?
ATPase activity
what does slow axonal transport carry?
cytosolic and cytoskeletal proteins and enzymes for small neurotransmitter synthesis from soma to axon terminal
what’s the mechanism of slow axonal transport?
- v.slow
- uses diffusion
- stop and go– fast movement but prolonged pauses
what 4 factors govern the rate of axonal transport?
- cargo
- type of motor
- number of stops
- changing of motor/tracks