Post-Translational Incorporation of L-Phenylalanine into the C-Terminus of alpha-Tubulin as a Possible Cause of Neuronal Dysfunction

DITAMO, Y; DENTESANO, YM; PURRO, SA; ARCE, CA; BISIG, CG

Scientific Reports

Nature Publishing Group

Año: 2016

#945;-Tubulin C-terminus undergoes post-translational, cyclic tyrosination/detyrosination, andL-Phenylalanine (Phe) can be incorporated in place of tyrosine. Using cultured mouse brain-derivedcells and an antibody specific to Phe-tubulin, we showed that: (i) Phe incorporation into tubulin isreversible; (ii) such incorporation is not due to de novo synthesis; (iii) the proportion of modifiedtubulin 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) thisinhibitory effect of Phe on neurite retraction is blocked by the co-presence of tyrosine; (vii) microtubuledynamics is reduced when Phe-tubulin level in cells is high as a result of exogenous Phe addition andreturns to normal values when Phe is removed; moreover, microtubule dynamics is also reduced whenPhe-tubulin is expressed (plasmid transfection). It is known that Phe levels are greatly