Articulo
Functional role of the disulfide isomerase ERp57 in axonal regeneration
PLOS ONE
Registro en:
1150608
1150608
Autor
Castillo, Valentina
Oñate, Maritza
Woehlbier, Ute
Rozas, Pablo
Andreu, Catherine
Medinas, Danilo
Valdes, Pamela
Osorio, Fabiola
Mercado, Gabriela
Vidal-Gómez, René Luis
Kerr, Bredford
Court-Goldsmith, Felipe Alfredo
Hetz, Claudio
Institución
Resumen
ERp57 (also known as grp58 and PDIA3) is a protein disulfide isomerase that catalyzes disulfide bonds formation of glycoproteins as part of the calnexin and calreticulin cycle. ERp57 is markedly upregulated in most common neurodegenerative diseases downstream of the endoplasmic reticulum (ER) stress response. Despite accumulating correlative evidence supporting a neuroprotective role of ERp57, the contribution of this foldase to the physiology of the nervous system remains unknown. Here we developed a transgenic mouse model that overexpresses ERp57 in the nervous system under the control of the prion promoter. We analyzed the susceptibility of ERp57 transgenic mice to undergo neuro-degeneration. Unexpectedly, ERp57 overexpression did not affect dopaminergic neuron loss and striatal denervation after injection of a Parkinson's disease-inducing neurotoxin. In sharp contrast, ERp57 transgenic animals presented enhanced locomotor recovery after mechanical injury to the sciatic nerve. These protective effects were associated with enhanced myelin removal, macrophage infiltration and axonal regeneration. Our results suggest that ERp57 specifically contributes to peripheral nerve regeneration, whereas its activity is dispensable for the survival of a specific neuronal population of the central nervous system. These results demonstrate for the first time a functional role of a component of the ER proteostasis network in peripheral nerve regeneration.
Keywords. KeyWords Plus:UNFOLDED PROTEIN RESPONSE; AMYOTROPHIC-LATERAL-SCLEROSIS; ENDOPLASMIC-RETICULUM STRESS; PARKINSONS-DISEASE; SCHWANN-CELLS; NEURODEGENERATIVE DISEASES; MISFOLDED PROTEINS; NERVE REGENERATION; SENSOR IRE1-ALPHA; PERIPHERAL-NERVE Regular 2015 FONDECYT FONDECYT