Irreversible incorporation of L-dopa into the C-terminus of -tubulin inhibits binding of molecular motor KIF5B to microtubules and alters mitochondrial traffic along the axon

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

NEUROBIOLOGY OF DISEASE

ACADEMIC PRESS INC ELSEVIER SCIENCE

Lugar: Amsterdam; Año: 2021

0969-9961

-dopa is the most effective drug used to date for management of Parkinson´sdisease symptoms. Unfortunately, long-term administration of L-dopa often results indevelopment of motor disorders, including dyskinesias. Despite extensive researchon L-dopa-induced dyskinesia, its pathogenesis remains poorly understood. Wedemonstrated previously that L-dopa can be post-translationally incorporated into theC-terminus of α-tubulin in living cells. In the present study, we investigated the effectof the presence of L-dopa-tubulin-enriched microtubules on mitochondrial trafficmediated by molecular motor KIF5B. Using biochemical approaches in combinationwith experiments on neuronal cell lines and mouse hippocampal primary cultures, wedemonstrated that L-dopa incorporation into tubulin is irreversible. Transport ofmitochondria along the axon was altered after L-dopa treatment of cells. In L-dopa-treated cells, mitochondria had reduced ability to reach the distal segment of theaxon, spent more t