Long-distance retrograde neurotrophic factor signalling in neurons

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Abstract

The specialized architecture of neurons necessitates unique modes of intracellular communication to allow for cell survival, the ability to detect and respond to injury and aspects of neuronal development, such as axon and dendrite growth, plasticity, and synapse and circuit formation. Many of these neuronal processes rely on signal transduction pathways and transcriptional programmes that are activated by retrograde signals originating from target-derived cues that act on distal axons. Here, we review the many functions of long-range distal axon-to-cell body signalling and discuss mechanisms of retrograde target-derived growth factor signalling.

Key Points

  • Neurons require specialized mechanisms of intracellular neurotrophic factor signalling for communication over the long distances between axon terminals and the nucleus.

  • Retrograde neurotrophic factor signalling is essential for neuronal survival, axon and dendrite growth, neuronal subtype specification and synapse formation.

  • Mechanisms of retrograde signalling may vary for different ligand–receptor systems; for neurotrophins, retrograde signalling occurs through an internalized vesicle containing ligand and receptor — an entity termed the 'signalling endosome'.

  • Emerging evidence indicates that defects in trafficking and axonal transport of crucial retrograde trophic factor signals contribute to the pathology of several neurodegenerative diseases.

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Figure 1: Retrograde signals controlling sensory neuron development.
Figure 2: Retrograde NGF signalling controls sympathetic neuron survival and connectivity.
Figure 3: Mechanisms of neurotrophin internalization, signalling and retrograde transport.

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Acknowledgements

We thank members of the Ginty laboratory for their helpful comments and suggestions during the preparation of this manuscript.

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Correspondence to David D. Ginty.

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Glossary

Neurotrophic factor hypothesis

Neurons are overproduced during development. The neurotrophic factor hypothesis states that neurons that successfully compete for limiting amounts of target-derived survival factor gain a competitive advantage over others and survive, whereas those that fail to compete die.

Retrograde transport

The directed, coordinated movement of proteins or vesicles from distal axons towards the neuronal soma.

Signalling endosome

A term referring to endosomes containing active ligand–receptor complexes that associate with and activate components of downstream growth and survival signalling pathways as they traffic within axons and cell bodies.

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