Artículo
Post-translational incorporation of L-Phenylalanine into the C-Terminus of alpha-Tubulin as a possible cause of neuronal dysfunction
Ditamo, Yanina
; Dentesano, Yanela Melani
; Purro, Silvia Amneris
; Arce, Carlos Angel
; Bisig, Carlos Gaston
Fecha de publicación:
12/2016
Editorial:
Nature Publishing Group
Revista:
Scientific Reports
ISSN:
2045-2322
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
α-Tubulin C-terminus undergoes post-translational, cyclic tyrosination/detyrosination, and L-Phenylalanine (Phe) can be incorporated in place of tyrosine. Using cultured mouse brain-derived cells and an antibody specific to Phe-tubulin, we showed that: (i) Phe incorporation into tubulin is reversible; (ii) such incorporation is not due to de novo synthesis; (iii) the proportion of modified tubulin is significant; (iv) Phe incorporation reduces cell proliferation without affecting cell viability; (v) the rate of neurite retraction declines as level of C-terminal Phe incorporation increases; (vi) this inhibitory effect of Phe on neurite retraction is blocked by the co-presence of tyrosine; (vii) microtubule dynamics is reduced when Phe-tubulin level in cells is high as a result of exogenous Phe addition and returns to normal values when Phe is removed; moreover, microtubule dynamics is also reduced when Phe-tubulin is expressed (plasmid transfection). It is known that Phe levels are greatly elevated in blood of phenylketonuria (PKU) patients. The molecular mechanism underlying the brain dysfunction characteristic of PKU is unknown. Beyond the differences between human and mouse cells, it is conceivable the possibility that Phe incorporation into tubulin is the first event (or among the initial events) in the molecular pathways leading to brain dysfunctions that characterize PKU.
Palabras clave:
Tubulin
,
Microtubules
,
Phenylalanine
,
Phenylketonuria
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Articulos(CIQUIBIC)
Articulos de CENTRO DE INVEST.EN QCA.BIOL.DE CORDOBA (P)
Articulos de CENTRO DE INVEST.EN QCA.BIOL.DE CORDOBA (P)
Citación
Ditamo, Yanina; Dentesano, Yanela Melani; Purro, Silvia Amneris; Arce, Carlos Angel; Bisig, Carlos Gaston; Post-translational incorporation of L-Phenylalanine into the C-Terminus of alpha-Tubulin as a possible cause of neuronal dysfunction; Nature Publishing Group; Scientific Reports; 6; 3814; 12-2016; 1-11
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