Plasticity Related Gene 3 (PRG3) overcomes myelin‐associated growth inhibition and promotes functional recovery after spinal cord injury

AGING (Albany NY), 2016 · DOI: · Published: October 15, 2016

Spinal Cord Injury Neurology Neuroplasticity

Simple Explanation

The Plasticity Related Gene family covers five, brain‐specific, transmembrane proteins (PRG1‐5, also termed LPPR1‐5) that operate in neuronal plasticity during development, aging and brain trauma. Here we investigated the role of the PRG family on axonal and filopodia outgrowth. Comparative analysis revealed the strongest outgrowth induced by PRG3 (LPPR1). During development, PRG3 is ubiquitously located at the tip of neuronal processes and at the plasma membrane and declines with age. PRG3-induced neurites resist brain injury-associated outgrowth inhibitors and contribute to functional recovery after spinal cord lesions. Here, we provide evidence that PRG3 operates as an essential neuronal growth promoter in the nervous system.

Study Duration

Not specified

Participants

Mice and cell lines

Evidence Level

Not specified

Key Findings

1
PRG3 induces the formation of filopodia and promotes axonal growth.
2
The neurite growth promoting activity of PRG3 requires RasGRF1 (RasGEF1/Cdc25) mediated downstream signaling.
3
PRG3-induced neurites resisted growth inhibitors such as myelin, Nogo‐A (Reticulon/RTN‐4), thrombin and LPA and impeded the RhoA‐Rock‐PIP5K induced neurite repulsion.

Research Summary

The Plasticity Related Gene family covers five, brain‐specific, transmembrane proteins (PRG1‐5, also termed LPPR1‐5) that operate in neuronal plasticity during development, aging and brain trauma. Comparative analysis revealed the strongest outgrowth induced by PRG3 (LPPR1). Transgenic adult mice with constitutive PRG3 expression displayed strong axonal sprouting distal to a spinal cord lesion.

Practical Implications

Therapeutic Potential

PRG3 emerges as a potential target for therapeutic interventions due to its ability to counteract the neurite growth inhibitory action of PIP5K.

Spinal Cord Injury Treatment

PRG3 impedes neuronal growth restriction in vivo and fosters functional regeneration in the adult central nervous system, suggesting its potential use in spinal cord injury treatment.

Aging Brain Regeneration

Maintaining PRG3 expression in aging brain may turn back the developmental clock for neuronal regeneration and plasticity.

Study Limitations

1
Whether PRG3 regulates synaptic transmission needs to be further investigated.
2
Further investigations will focus on the deletion of the prg3 gene at the genomic level to open such studies in vivo.
3
Further functional data in vivo is needed.

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