NEUS 609 - Axonal Transport

99

___ of nerve cell matter/volume is the axon as it usually travels long distances

bidirectional

axonal transport is observed to be ___, not fully continuous, and about of equal speed both ways

anterograde

AWAY from the cell body

• usually transport vesicles precursors, peptide neurotransmitters, dense vesicles, mitochondria, and golgi (only in dendrites)

retrograde

TOWARD the cell body

• usually transport organelles that are to be recycled, viruses, trophic factors, and endosomal vesicles

molecular motors

mechanochemical enzymes changing conformation using the energy from ATP hydrolysis to produce movement. Require attachment to cytoskeleton elements.

• myosin

• kinesin

• dynein

myosin

molecular motor protein binding to microfilaments to produce movement and muscle contraction

kinesin

molecular motor protein binding to microtubule to provide intracellular transport

• tetramer made of 2 heavy chains & 2 light chains

• walks toward the positive end of microtubules (in axon, anterograde transport ONLY)

motor domains

the 2 heavy chains in kinesin and dynein are where the ___ are located and what bind to the microtubules

dynein

molecular motor protein binding to microtubule to provide intracellular transport

• 2 types: cytoplasmic & axonemal

• 12 protein dimers (2 heavy chains & multiple light chains)

• cannot bind cargo without dynactin complex

• move toward the negative end of microtubules (in axon, RETROGRADE ONLY)

cytoplasmic

__ dynein = intracellular trasnport

axonemal

__ dynein movement of cilia and flagella

dynactin

one of the 2 complexes making up dynein; the one binding cargo protein and also helping attach to microtubules

• 2 major dimers (microtubule attachment) & 23 linker proteins (cargo binding)

clockwise, counterclockwise

microtubules polarity is decided by the direction of their hooks, which dictate direction of transport of molecular motors.

• __ = positive end

• __ = negative end

mixed

microtubules in dendrites have ___ polarity, leading to bidirectional transport

herpes virus

1. infect epithelial cell and do lytic cycle to make new viruses

2. new viruses’ uptake by sensory neurons and retrograde transport toward cell soma where it lies dormant

3. recurrent infection due to virus being occasionally reactivated and anterogradely transported to terminal and released 

fast transport

• bidirectional

• anterograde OR retrograde

• usually vesicles, neuropeptides, mitochondria OR recycled organelles and endosomes

slow transport

• unidirectional

• ANTEROGRADE ONLY

• transport cytoskeleton elements like microtubules and neurofilaments

neurofilament transport

• kinesin

• depends on phosphorylation

  • PHOSPHORYLATED = greater affinity for stable neurofilament = PAUSE

  • NON-PHOSPHORYLATED = greater affinity for kinesin = MOVE

microtubule transport

• dynein

• dynein fix itself on actin filaments instead of cargo, so when the motor domains change conformation and move it just scoot the microtubule forward/anterogradely.

radioisotope

axonal transport was discovered using ___ labeling