Alpha synuclein induces differential effects in protein intracellular trafficking

OVEJERO M; BISBAL M; CACERES A; ANASTASIA A

Santa cruz

Workshop; 2023 IUBMB EMBO Workshop Emerging Concepts of the Neuronal Cytoskeleton; 2023

IUBMB y EMBO

Alpha synuclein (AS) is a widely studied protein for its role in different neurodegenerative diseasessuch as Parkinson's disease and a group of pathologies called synucleinopathies. Despite being thefocus of several studies, its normal function it is still partly unknown and the manner in which thisprotein is involved in neuronal death is still not fully elucidated. One of the most interesting hypothesissuggests that AS might be affecting the intracellular vesicle trafficking and consequently affectingneuronal survival (Cooper AA 2006; experiments in yeast). Our focus is to study the effects of AS onthe intracellular trafficking in mammalian neurons and the impact on neuronal structure and function.For this aim, we use the FM exocytic pathway synchronization system to analyze the effect of AS onprotein trafficking dynamics in cultured neurons. We found that AS reduces protein trafficking from theGolgi apparatus to neuronal processes, but not in a general way. Instead, our results show that ASaffects p75NTR trafficking, while it does not have an impact on Transferrin Receptor. Interestingly, ASalters p75NTR vesicles TGN fission, but not the Transferrin Receptor. Our preliminary findings suggestthat AS modifies the actin cytoskeleton dynamics, and we propose that this effect is a potentialmechanism for the altered trafficking detected. These findings shed light on the mechanism by whichAS may be acting in neurodegenerative diseases.