Posttranslational modification of tubulin by tyrosine analogues alters mitochondrial transport mediated by molecular motors

ZORGNIOTTI A; FILIBERTI, V; DITAMO Y; ARCE CA; BISIG CG

Carlos Paz

Congreso; XXXIV Reunion Anual de la Sociedad Argentina de Investigacion en Neurociencias; 2019

Sociedad Argentina de Investigación en Neurociencias

The C-terminal tyrosine (Tyr) of the α-tubulin chain is subjected to post-translational removal and re-addition in a process termed the detyrosination/tyrosination cycle. We showed in previous studies, using soluble rat brain extracts, that L-3,4-dihydroxyphenylalanine (L-Dopa) and L-phenylalanine (Phe) are incorporated into the same site as Tyr and that such incorporation also occurs in living cells. To study the functional effects of the incorporation of Tyr analogues into α-tubulin, we treated primary rat hippocampal neurons with L-Dopa or Phe. We observed a reduction in the number of mitochondria in distal segments of the axon and alterations in the mitochondrial traffic along axonal microtubules. We also observed an abnormal interaction between L-Dopa enriched microtubules and molecular motors that participate in organelles transport. We hypothesized that this alterations could be associated with neuronal disorders observed in Phenylketonuria patients and Parkinson?s disease patients treated with L- Dopa for prolonged periods.