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Microtubule dynamics at synaptic contacts are modulated by neuronal activity and affected by oligomeric Aβ 1-42

Mardi 7 janvier 11:30 - Duree : 1 heure
Lieu : Amphithéâtre Serge Kampf, Grenoble Institut des Neurosciences (GIN) - Bât. Edmond J. Safra, Chemin Fortune Ferrini CHU, La Tronche

Orateur : Francesca BARTOLINI (Columbia University Medical Center, New York)

Emerging studies from several groups have indicated that dynamic microtubules (MTs), in addition to modified MTs, play key roles in neuronal function. In addition, synaptic biphasic fluctuations of MT instability/stability and tubulin post-translational modifications (PTMs) are associated with memory formation and are disrupted in aging, indicating a primary role for the regulation of MT dynamics and tubulin PTMs in the maintenance of synaptic plasticity. In support of this model, we recently found that stabilization of dynamic MTs and induction of tubulin PTMs by the formin mDia1 contribute to oligomeric Aβ 1-42 synaptotoxicity, and inhibition of MT dynamics alone is sufficient to promote tau hyperphosphorylation and tau dependent synaptotoxicity (Qu et al., J Cell Biol, 2017). To test whether these changes occur at synapses and are directly responsible for synapse loss, we have further developed microscopy assays that measure MT invasions into dendritic spines and MT contacts with single presynaptic boutons of hippocampal neurons in culture. Surprisingly, we found that dynamic MT plus ends preferentially grow near presynaptic boutons, and res-cue/nucleation at boutons is enhanced by neurotransmitter release or when neurons are challenged with oligomeric Aβ1-42 (Aβ), an activity mediated by tau. Aβ also acutely affected the fraction of spines invaded by MTs, which appeared to be the most resistant to injury-dependent structural plas-ticity. Our data underscore the existence of a previously uncharacterized pool of presynaptic dynam-ic MTs that respond to neurotransmission and excitotoxicity, and reveal a function for spine-invading MTs in conferring resistance to pruning.

Contact : leticia.paris@univ-grenoble-alpes.fr

Discipline évènement : (Biologie / Chimie)
Entité organisatrice : (GIN)
Nature évènement : (Séminaire)
Evènement répétitif : (Séminaire Grenoblois de Neurosciences)
Site de l'évènement : Pôle Santé / La Tronche

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