Symposium: Cytoskeleton, its alterations, and neuronal defects. Chair: G Bisig

C. GASTÓN BISIG

Simposio; Congreso SAN 2021; 2021

Symposium: α-tubulin c-terminal modification: the importance of being tyrosinated.Summary: The C-terminal tyrosine (Tyr) of the α-tubulin chain is subjected to post-translationalremoval and readdition in a process termed the "detyrosination/tyrosination cycle". L-Dopa andL-Phenylalanine (Phe) can be incorporated into tubulin in place of tyrosine. We described thatthe presence of L-Dopa in tubulin affects microtubules dynamics, mitochondrial traffic, andKIF5B affinity for Dopa-tubulin-containing microtubules. These findings could be relevant for theneuronal defects observed in Parkinson´s disease patients treated with L-dopa for long periodsof time.When Phe was the analogue incorporated into tubulin, we observed that not only microtubulesdynamics and mitochondrial traffic were altered, but in this case neurites retraction and cellproliferation were also affected. Since it is known that Phe is increased in phenylketonuria, it isconceivable the possibility that Phe incorporation into tubulin is the first event (or among theinitial events) in the molecular pathways leading to brain dysfunctions that characterize thisneurological disorder.We found that, even though the analogues of Tyr incorporated into tubulin are different, theysimilarly affect neuronal microtubules functions, and this raises the question whether thesealterations are caused by the analogue presence by itself or by disbalancing thedetyrosinated/tyrosinated tubulin content.