Communication is everything
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- The longest cells in the body are neurons (up to a meter in large mammals).
- Intracellular communication and transport are therefore extremely complex.
- It is essential to understand them in order to find valid therapeutic targets for promoting regeneration after injury.
- Dr. Fainzilber gives an overview of the actual knowledge of intracellular communication after injury.
Dr. Fainzilber and Dr. Ida Rishal recently published a review summarizing the current knowledge of intracellular communication after an injury. This review appeared in the prestigious Nature Review Neuroscience journal.
A neuron has typically few tens of micrometers in diameter. This means that the ratio of the neuron length to its cell body is about 100.00 to 1. Neurons require complex mechanisms to allow intracellular communication to reach such length. This phenomenon is particularly important in case of nerve injury, such as after spinal cord injury. The distal segments of injured axons are eliminated by degeneration (see figure) and neurons must regenerate the lost process in its entirety.
Before starting to attempt a regrowth the neuron must become aware of its distant axonal injury. This is accomplished by two temporal phases. First, a wave of intracellular calcium starts almost immediately and reaches the cell body within a few minutes. This early phase is extremely important as it triggers auto-reparation mechanisms locally, before the information has reached the main cell body. After the first wave of ion-flux-based signals, there is a later and somewhat delayed phase of retrograde signaling to the cell body that is mediated by macromolecular signaling complexes. This second phase is far more complex and the neuron needs to integrate several signals in order to start the proper repair mechanisms (see figure).
The multiplicity of retrograde injury signaling molecules probably ensures robustness in the system. But this also inflicts a further challenge to the scientists who are willing to manipulate it in order to activate axonal regeneration. Indeed, manipulating a single pathway might have very little impact on the overall cellular behavior. Scientists are currently seeking so-called “regulatory hubs” where multiple pathways converge, offering more suitable therapeutic targets to promote regeneration (see figure).
Understanding such mechanisms is essential also for promoting neuronal regeneration in chronic injuries, months or years after the actual spinal cord injury.
Article: Axon-soma communication in neuronal injury. Rishal I, Fainzilber M. Nat Rev Neurosci. 2014 Jan;15(1):32-42.
About the author:
Dr. Mike Fainzilber works at the Department of Biological Chemistry, within the Weizmann Institute of Science in Israel. His project explores the idea that axons from the central nervous system fail to regenerate because they have a deficit in retrograde injury signaling caused by lack of importin β1. For more information on Dr. Fainzilber’s current project please visit the following page.
Graphics: Vieri Failli / Wings for Life