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Camin DEAN "Function of synaptotagmin isoforms on both sides of the synapse."

Abstract :


The synaptotagmins (syts) are a family of molecules that regulate membrane fusion.
There are seventeen mammalian syt isoforms, most of which are expressed in the brain. However, little is known regarding the subcellular location and function of the majority of these syts in neurons. Interestingly, only syt-1 and 2 are targeted to synaptic vesicles, while other isoforms selectively recycle in dendrites, axons, or in both axons and dendrites, where they undergoexo- and endocytosis with distinctive kinetics. Syt isoforms thus appear to localize to distinct secretory organelles in both axons and dendrites, and may regulate exocytosis on both sides of the synapse to modulate neuronal function.

Selected publications

Distinct subsets of Syt-IV/BDNF vesicles are sorted to axons versus dendrites and recruited to synapses by activity. Dean C, Liu H, Staudt T, Stahlberg MA, Vingill S, Bückers J, Kamin D, Engelhardt J, Jackson MB, Hell SW, Chapman ER. J Neurosci. 2012 Apr 18;32(16):5398-413.

Zhang G, Bai H, Zhang H, Dean C, Wu Q, Li J, Guariglia S, Meng Q, Cai D (2011) Neuropeptide exocytosis involving synaptotagmin-4 and oxytocin in hypothalamic programming of body weight and energy balance. Neuron 69(3):523-35

Lee H, Dean C, Isacoff E (2010) Alternative splicing of neuroligin regulates the rate of presynaptic differentiation. J Neurosci 30(34):11435-46

Arthur CP, Dean C, Pagratis M, Chapman ER, Stowell MH (2010) Loss of synaptotagmin IV results in a reduction in synaptic vesicles and a distortion of the Golgi structure in cultured hippocampal neurons. Neuroscience 167(1):135-42

Dean C, Scheiffele P (2009) Imaging synaptogenesis by measuring accumulation of synaptic proteins. In Imaging in Developmental Biology: A Laboratory Manual. Cold Spring Harbor Protocols. R. Wong, J. Sharpe and R. Yuste eds. (11):pdb.prot5315

Liu, H, Dean, C, Arthur, CP, Dong, M, Chapman, ER (2009) Autapses and networks of hippocampal neurons exhibit distinct synaptic transmission phenotypes in the absence of synaptotagmin I. J. Neurosci 29(23):7395-403

Scientific focus :

Our lab is interested in the mechanisms by which individual synapses, neurons and circuits dynamically adjust their transmission properties in response to changes in neuronal network activity. To accomplish this, neurons signal to eachother not only unidirectionally via classical pre to post-synaptic transmission, but also bidirectionally via pre or post-synaptic release of neuropeptides and neurotrophins. This bidirectional channel of communication is essential for the modulation of synapse and circuit strength, via regulation of distinct membrane fusion events on both sides of the synapse, including synaptic vesicle exocytosis, post-synaptic receptor recycling, and adhesion molecule recycling. We investigate the mechanisms by which these trans-synaptic signaling events are regulated, at the level of single synapses, single neurons and neuronal networks, using a combination of live imaging approaches, electrophysiology, and biochemistry in neuronal cell culture and brain slices. Our overall goal is to understand how neurons communicate changes in activity to affect circuit function, and ultimately behavior, during learning and memory acquisition, or to counteract aberrant brain states such as seizure activity.

David Perrais de l'IINS