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.

Proteolytic control of neurite outgrowth inhibitor NOGO-A by the cAMP/PKA pathway / Sepe, Maria; Lignitto, L; Porpora, M; Delle Donne, R; Rinaldi, Laura; Belgianni, G; Colucci, G; Cuomo, Ornella; Viggiano, D; Scorziello, Antonella; Garbi, Corrado; Annunziato, Lucio; Feliciello, Antonio. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - 111:44(2014), pp. 15729-15734. [10.1073/pnas.1410274111]

Proteolytic control of neurite outgrowth inhibitor NOGO-A by the cAMP/PKA pathway

SEPE, MARIA;RINALDI, LAURA;CUOMO, ORNELLA;SCORZIELLO, ANTONELLA;GARBI, CORRADO;ANNUNZIATO, LUCIO;FELICIELLO, ANTONIO
2014

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.
2014
Proteolytic control of neurite outgrowth inhibitor NOGO-A by the cAMP/PKA pathway / Sepe, Maria; Lignitto, L; Porpora, M; Delle Donne, R; Rinaldi, Laura; Belgianni, G; Colucci, G; Cuomo, Ornella; Viggiano, D; Scorziello, Antonella; Garbi, Corrado; Annunziato, Lucio; Feliciello, Antonio. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - 111:44(2014), pp. 15729-15734. [10.1073/pnas.1410274111]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/602051
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