Proteolytic control of neurite outgrowth inhibitor NOGO-A by the cAMP/PKA pathway.
Proc Natl Acad Sci U S A
; 111(44): 15729-34, 2014 Nov 04.
Article
em En
| MEDLINE
| ID: mdl-25331889
ABSTRACT
Protein kinase A (PKA) controls major aspects of neurite outgrowth and morphogenesis and plays an essential role in synaptic plasticity and memory. However, the molecular mechanism(s) of PKA action on neurite sprouting and activity are still unknown. Here, we report that in response to neurotrophin or cAMP stimulation the RING ligase praja2 ubiquitinates and degrades NOGO-A, a major inhibitor of neurite outgrowth in mammalian brain. Genetic silencing of praja2 severely inhibited neurite extension of differentiating neuroblastoma cells and mesencephalic neurons and axon outgrowth and sprouting of striatal terminals in developing rat brain. This phenotype was rescued when both praja2 and NOGO-A were depleted, suggesting that NOGO-A is, indeed, a biologically relevant target of praja2 in neuronal cells. Our findings unveil a novel mechanism that functionally couples cAMP signaling with the proteolytic turnover of NOGO-A, positively impacting on neurite outgrowth in mammalian brain.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Mesencéfalo
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Neuritos
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Proteínas Quinases Dependentes de AMP Cíclico
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AMP Cíclico
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Proteólise
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Proteínas da Mielina
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article