Axonal Transport
Brain and Nerves

Author: Gianpiero Pescarmona
Date: 01/03/2009


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


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

Mitochondria provide the Energy

Role of mitochondrial dynamics (fusion, fission and movement of mitochondria) in peripheral nerve disease:

Who provides the Fuel?

Molecular Motors

  • Kinesins complex proteins
    • Kinesin
  • Dynactin complex proteins
    • Dynactin
    • Dynein


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.


Role of Axonal Transport in Neurodegenerative Diseases 2008

2010-03-22T10:44:28 - Gianpiero Pescarmona

Papers BDNF Kinesin

Papers BDNF Dynein

2010-02-07T19:21:26 - Gianpiero Pescarmona

J Neurosci. 2009 Aug 5;29(31):9903-17.
A switch in retrograde signaling from survival to stress in rapid-onset neurodegeneration. 2009

Perlson E, Jeong GB, Ross JL, Dixit R, Wallace KE, Kalb RG, Holzbaur EL.

University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.

Retrograde axonal transport of cellular signals driven by dynein is vital for neuronal survival. Mouse models with defects in the retrograde transport machinery, including the Loa mouse (point mutation in dynein) and the Tg(dynamitin) mouse (overexpression of dynamitin), exhibit mild neurodegenerative disease. Transport defects have also been observed in more rapidly progressive neurodegeneration, such as that observed in the SOD1 transgenic mouse model for familial amyotrophic lateral sclerosis (ALS). Here, we test the hypothesis that alterations in retrograde signaling lead to neurodegeneration. In vivo, in vitro, and live-cell imaging motility assays show misregulation of transport and inhibition of retrograde signaling in the SOD1 model. However, similar inhibition is also seen in the Loa and Tg(dynamitin) mouse models. Thus, slowing of retrograde signaling leads only to mild degeneration and cannot explain ALS etiology. To further pursue this question, we used a proteomics approach to investigate dynein-associated retrograde signaling. These data indicate a significant decrease in retrograde survival factors, including P-Trk (phospho-Trk) and P-Erk1/2, and an increase in retrograde stress factor signaling, including P-JNK (phosphorylated c-Jun N-terminal kinase), caspase-8, and p75(NTR) cleavage fragment in the SOD1 model; similar changes are not seen in the Loa mouse. Cocultures of motor neurons and glia expressing mutant SOD1 (mSOD1) in compartmentalized chambers indicate that inhibition of retrograde stress signaling is sufficient to block activation of cellular stress pathways and to rescue motor neurons from mSOD1-induced toxicity. Hence, a shift from survival-promoting to death-promoting retrograde signaling may be key to the rapid onset of neurodegeneration seen in ALS.

Open Question: Role of SOD1 in axonal transport

Papers SOD1 mitochondria

Mutant SOD1 in neuronal mitochondria causes toxicity and mitochondrial dynamics abnormalities. 2009

(B) Relative motility of neuritic mitochondria from IMS-hSOD1 cells. n = 10–13 neurites, *P < 0.05, **P < 0.005 referred to mock-transfected cells. © Relative motility of neurite mitochondria in untargeted hSOD1 cells. n = 9–13 neurites, *P < 0.05, **P < 0.005 referred to mock control

Open Question: Role of inflammation in axonal transport


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