Development/Plasticity/Repair Caltubin, a Novel Molluscan Tubulin-Interacting Protein, Promotes Axonal Growth and Attenuates Axonal Degeneration of Rodent Neurons

Axotomized central neurons ofmost invertebrate species demonstrate a strong regenerative capacity, and as suchmay provide valuable molecular insights and new tools to promote axonal regeneration in injured mammalian neurons. In this study, we identified a novel molluscan protein, caltubin, ubiquitously expressed in central neurons of Lymnaea stagnalis and locally synthesized in regenerating neurites. Reduction of caltubin levels by gene silencing inhibits the outgrowth and regenerative ability of adult Lymnaea neurons and decreases local- and-tubulin levels in neurites. Caltubin binds to- and/or-tubulin in both Lymnaea and rodent neurons. Expres-sionof caltubin inPC12cells andmouse cortical neuronspromotesNGF-inducedaxonal outgrowthandattenuates axonal retractionafter injury. This is the first study illustrating that a xenoprotein can enhance outgrowth and prevent degeneration of injured mammalian neurons. These results may open up new avenues in molecular repair strategies through the insertion of molecular components of invertebrate regenerative pathways into mammalian neurons