IBCN   20355
INSTITUTO DE BIOLOGIA CELULAR Y NEUROCIENCIA "PROFESOR EDUARDO DE ROBERTIS"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Molecular mechanisms of axonal transport dynamics analyzed by fluorescent cargo tracking in mouse and human neuronal culture systems
Autor/es:
BESSONE, IVAN FERNANDEZ; HOLUBIEC MARIANA; FALZONE, TOMAS L.; SAEZ, TRINIDAD M. M.
Lugar:
Valdivia
Reunión:
Workshop; Cytoskeleton 2019, EMBO; 2019
Institución organizadora:
EMBO
Resumen:
The function and connectivity of highly polarized neurons depends on modulating the rates of proteins, vesicles and organelles intracellular delivery to distal synapses. Defects in axonal transport have been proposed as early igniter events of many neurodegenerative diseases. Therefore, is necessary to comprehend the intricate regulation of axonal transport dynamics that depends on highly regulated steps ranging from microtubule stability and their associated binding proteins, post-translational modifications of motors and cargo adaptor proteins by phosphorylation and de-phosphorylation, and modifiers proteins that allow engagement of active motors. Here we present different high resolution live imaging experiments performed in mouse and human neuronal cultures that allow the interpretation of different steps in axonal transport regulation. By calculating the Mean Square Displacement (MSD) of the proteasome complex as cargo trajectories in mouse neurons we demonstrated at least 3 modes of axonal transport that are relevant to homogeneously distribute proteasomes along axons. By extracting run lengths and instantaneous segmental velocities of APP vesicles in human neurons after modulating tau isoforms balance without overexpression, we uncover a physiological regulation of axonal dynamics of APP vesicles that can be associated with the developmental differential expression of tau isoforms. Finally, by the overexpression of Wt or mutant version of Synuclein protein we produced differential changes in axonal flux of mitochondria that can be linked with significant changes in mitochondrial morphology and clearance. Together, we present different steps of axonal transport regulation of cargo that build on a comprehensive molecular model that is relevant to understand the intricate mechanisms behind axonal cargo dynamics in health and disease.