CELL BIOLOGY OF THE NEURON Polarity ... - Tavernarakis Lab

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Cell Biology of the Neuron: Polarity, Plasticity and Regeneration, Crete 2011 Unraveling the Regulation of Intracellular Trafficking During the Establishment and Maintenance of Neuronal Polarity Joanna Chiang, Andreas W. Püschel Institut für Molekulare Zellbiologie, Schlossplatz 5 Westfälishe Wilhelm- Universität Münster, Germany The establishment of a polarized cell structure is essential for the differentiation, maturation and function of a neuron. The interplay of different signaling pathways and cell structures orchestrates the initiation of polarity in a neuron. It has been shown that increased bulk cytoplasmic flow into a neurite precedes its extension as the single axon. This observation highlights the importance of the transport machinery in neuronal polarity but little is known about how polarized transport into the nascent axon is initiated. Intracellular transport is also essential for the maintenance of polarity through its role in sorting proteins to axons and dendrites. Here we investigate members of the Rab family of GTPases that function as regulators of vesicular trafficking for their role in neuronal polarity. To identify Rabs potentially involved in neuronal polarity we screened a set of Rabs by expressing constitutively active and dominant-negative mutants in rat hippocampal neurons and analyzing the resulting phenotypes. We could identify several Rab GTPases that induce the formation of multiple axons when expressed in already polarized neurons. This analysis suggest a role for vesicle trafficking in the negative feedback that blocks the formation of supernumerary axons after polarity is established. By identifying Rab GTPases that act as regulators of endocytosis and vesicle trafficking, we hope to decipher how polarized transport is established, how it contributes to the maintenance of neuronal polarity. In parallel, we are investigating effectors downstream of these GTPases to unravel pathways that are linked to them. Together these experiments will lead to a better understanding of polarized transport and its regulation in neurons. Presented by: Chiang, Joanna Poster No 018 Blue Session 100
Cell Biology of the Neuron: Polarity, Plasticity and Regeneration, Crete 2011 Cellular Models to Explore Human Synaptogenesis Laurie Chicha 1 , Frederic Knoflach 1 , Rachel Haab 1 , Josef Bischofberger 2 , Roberto Iacone 3 , Bernd Bohrmann 1 , Martin Graf 3 , Sannah Jensen 3 , Ravi Jagasia 1 1 F. Hoffmann-La Roche Ltd - CNS Discovery 2 Institute for Physiology, University Basel 3 F. Hoffmann-La Roche Ltd - Discovery Technology A major challenge in CNS research is the establishment of cellular assays that accurately recapitulate normal and diseased neurophysiology in vitro. Synapses are fundamental structures in neuronal communication and the formation, remodeling and elimination of synapses are continual physiological processes. The relevance of synaptic homeostasis is highlighted by the fact that mutations in human post-synaptic density (PSD) proteins occur in over 100 neurological and psychiatric disorders. Here we aim to model human synaptogenesis in vitro using pluripotent stem cells. To this end, we characterize the physiologic and synaptic properties of two different neuronal subtypes differentiated from human embryonic stem cells, enriched in GABAergic or dopaminergic features. We describe the establishment of several assays to characterize synaptic properties including specific immunolabeling, electrophysiology and calcium imaging. We envision that such cellular models will be instrumental in the elucidation of mechanisms regulating human synaptic functions and in the future, we plan to extend our work to the modeling of pathophysiological mechanisms of synaptic dysfunction occurring in CNS diseases. Presented by: Chicha, Laurie 101 Poster No 019 Red Session
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The meeting was funded in part by E
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CYFIP1, a Neuronal eIF4E‐BP, Link
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POSTER ABSTRACTS Poster # [‐R(ed)
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030‐B Paracrine Pax6 Activity Reg
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058‐R Dynein Light Chain LC8 is a
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088‐R Spectraplakins ‐ Cytoskel
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121‐R Calmyrin1 Binds to SCG10 Pr
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18.00 ‐ 18.15 Non Hyperpolarizing
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10.00 ‐ 10.30 Neurotrophin Regula
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SESSION 10 SYNAPTOGENESIS Chairpers
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da F. Costa, L. 119 D'Adamo, P. 108
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Lewallen, K. 145 Li, Y.‐H. 201 Li
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Teuling, E. 141 Thiebes, K. 87 Thom
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Dr. Christian Alfano INSERM U636, N
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Prof. Graeme W. Davis University of
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Prof. Zhigang He Harvard Medical Sc
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Dr. Bernhard Lohkamp Karolinska Ins
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Mr. Abhishek Shrikant Sahasrabudhe
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