Axonal transport is a cellular process responsible for movement of mitochondria, lipids, synaptic vesicles, proteins, and other cell parts (i.e. organelles) to and from a neuron's cell body, through the cytoplasm of its axon (the axoplasm).
The vast majority of axonal proteins are synthesized in the neuronal cell body and transported along axons. Axonal transport occurs throughout the life of a neuron and is essential to its growth and survival.
Basic Neurochemistry- Axonal Transport
Transport is bi-directional
- anterograde
- fast (motor: kinesins complex proteins)
- slow
- retrograde
- fast (motor: dynactin complex proteins)
- some neurotropic viruses such as poliomyelitis, herpes, and rabies and neurotoxins that enter peripheral nerve endings and ascend to infect the cell body via retrograde transport.
- slow
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Axonal transport is very similar to fungal hyphae transport
Molecular Fungal Cell Biology
Microtubules provide the tracks.
Vesicles for transport are sorted and loaded onto transport motors both in the cell body and the distal nerve terminal.
The former are transported not only into the axon but also into dendrites.
Those in the distal nerve terminal permit uptake and axosomatic movement of substances such as trophic proteins.
Mutations in dynactin (humans), dynein (mice) and three different forms of kinesin all provoke motor neuron degeneration. Perturbation of neurofilaments through mutations and changes in phosphorylation and the physical structure of the axon could also adversely affect axonal transport. In transgenic mouse models, mutant superoxide dismutase 1 (SOD1) impairs anterograde axonal transport.
Active Dendrites in Motor Neurons 2004
Role of mitochondrial dynamics (fusion, fission and movement of mitochondria) in peripheral nerve disease:
Who provides the Fuel?
Molecular Motors
- Kinesins complex proteins
- Dynactin complex proteins
REGULATION OF DIRECTION
Huntingtin phosphorylation acts as a molecular switch for anterograde/retrograde transport in neurons. 2008 Fulltext
EMBO J. 2008 Aug 6;27(15):2124-34. Epub 2008 Jul 10.
Colin E, Zala D, Liot G, Rangone H, Borrell-Pagès M, Li XJ, Saudou F, Humbert S.
Institut Curie, Orsay, France.
The transport of vesicles in neurons is a highly regulated process, with vesicles moving either anterogradely or retrogradely depending on the nature of the molecular motors, kinesins and dynein, respectively, which propel vesicles along microtubules (MTs). However, the mechanisms that determine the directionality of transport remain unclear. Huntingtin, the protein mutated in Huntington's disease, is a positive regulatory factor for vesicular transport. Huntingtin is phosphorylated at serine 421 by the kinase Akt but the role of this modification is unknown. Here, we demonstrate that phosphorylation of wild-type huntingtin at S421 is crucial to control the direction of vesicles in neurons. When phosphorylated, huntingtin recruits kinesin-1 to the dynactin complex on vesicles and MTs. Using brain-derived neurotrophic factor as a marker of vesicular transport, we demonstrate that huntingtin phosphorylation promotes anterograde transport. Conversely, when huntingtin is not phosphorylated, kinesin-1 detaches and vesicles are more likely to undergo retrograde transport. This also applies to other vesicles suggesting an essential role for huntingtin in the control of vesicular directionality in neurons.
Figure
Role of Axonal Transport in Neurodegenerative Diseases 2008
