Novel signaling pathways underlying the effects of mitochondria on neuronal morphogenesis and synaptic function
Mercredi 27 avril 2016 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 : Franck POLLEUX (Columbia University, New York)
We recently identified a new kinase pathway defined by LKB1 and another of its 14 direct downstream kinases called NUAK1 as critical regulators of cortical axon branching in vivo (Courchet, Lewis, et al. 2013). Our results show for the first time that the LKB1-NUAK1 kinase pathway is both necessary and sufficient for controlling the arborization of developing axons through a novel cell biological step : presynaptic mitochondrial capture. We are now exploring two important questions raised by this work : (1) how presynaptic mitochondria regulates axon development ? and (2) what anchors mitochondria at presynaptic sites along CNS axons ?
In my seminar, I will show results pertaining to the first question. In addition to be essential for ATP production, mitochondria are also central in buffering cytoplasmic Ca2+ through an inner-membrane calcium channel called Mitochondrial Calcium Uniporter. Our most recent results show that LKB1 governs the capacity of mitochondria to uptake calcium at presynaptic sites (Kwon et al. 2015 in revision). Loss of LKB1 activity significantly reduces the numbers of presynaptic mitochondria and alters their Ca2+ clearance properties. These deficiencies result in increased Ca2+ build-up during synaptic stimulation and drastically alter the efficacy and kinetics of neurotransmitter release. Based on these findings, we propose that LKB1-dependent presynaptic mitochondrial capture plays a previously unidentified and critical role during axon branching by regulating local calcium homeostasis and synaptic transmission.
Contact : frédéric.saudou@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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