Saptaparna Pal, Amity University Kolkata
Axons of the adult peripheral nervous system(PNS) and immature central nervous system (CNS) neurons readily regenerate after injury. In addition to the non-permissive extracellular environment after injury, the intrinsic neuronal factors also play an important role in the regenerative failure that is observed in mature CNS neurons.
Protrudin acts as a tool for investigating and enhancing axon growth and regeneration in adult CNS. Protrudin is an integral endoplasmic reticulum (ER) membrane protein that has two properties which makes it an applicant for allowing axon regeneration. One being a scaffolding molecule that possesses interaction sites for key axon growth-related structures.
The ER localizes to the Protrudin through two transmembrane domains and a hairpin loop and interacts with the VAP proteins at ER membrane contact sites through the FFAT domain. Overexpression of Protrudin, specifically in its phosphomimetic form, led to neuro protein of mature cortical axons in vitro and of retinal ganglion cells (RCG) axons in the injured optic nerves. Protrudin also gets expressed at low levels in mature, nongenerative CNS neurons. Regenerative effects of Protrudin were mediated through enhanced axonal transport. The exclusion of the growth-related molecules from the mature axons is one of the reasons for the failure of Protrudin to regenerate and restoration of RabII vesicle and integrins to mature axons can restore regeneration.
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Source link: Petrova, V., Pearson, C.S., Ching, J. et al. Protrudin functions from the endoplasmic reticulum to support axon regeneration in the adult CNS. Nat Commun 11, 5614 (2020). https://doi.org/10.1038/s41467-020-19436-y
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