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

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Cell Biology of the Neuron: <strong>Polarity</strong>, Plasticity and Regeneration, Crete 2011 Regulation of Neurofibromin RasGAP Activity and Localization during Neuronal Differentiation George Leondaritis 1 , Theodora Kalpachidou 2 , Dimitra Mangoura 2 1 Department of Pharamcology, Medical School, University of Thessaly, Larissa, Greece 2 Neurosciences, Biomedical Research Foundation Academy of Athens, Athens, Greece Ras and ERK1/2 signalling is pivotal to differentiation along the neuronal cell lineage. One crucial protein that may play a central role in this signalling pathway is the tumor suppressor RasGAP, neurofibromin (NF1). By studying the dynamics of PKC/Ras/ERK pathway signalling during differentiation of neuroblastoma cells upon treatment with a PKC agonist, we identified a phosphorylation event at the C-tail of NF1 on Ser2808 which correlated perfectly with acute and prolonged activation of Ras and ERK1/2. Importantly, Ser2808 phosphorylation resulted in a shift of NF1 localization from the nucleus to the cytosol and mutation to Ala caused reduced PKC-dependent phosphorylation and increased nuclear localization of the NF1-C-terminal domain. Thus, sustained Ser2808 phosphorylation may result in prolonged recruitment of nuclear NF1 to cytosolic membranous Ras complexes. In search for NF1 domains that may confer cytosolic, cytoskeletal or vesicular localization we focused on a Sec14homology domain adjacent to GRD, the central RasGAP domain. Overexpressed Sec14 and GRD+Sec14 had a microtubule-associated and vesicular localization pattern reminiscent of the endogenous cytosolic pool of NF1 in differentiated neurons and COS-7 cells. Most importantly however, Sec14 induced an upregulation of RasGAP activity of GRD in vivo presumably by atypical direct interactions with Ras. A detailed kinetic analysis of NF1-GRD and NF1- GRD+Sec14 activities in EGF-stimulated cells suggested that Sec14 imposed a digital-like mode on the analog GAP activity of GRD. Thus, distinct NF1 domains regulated by distinct mechanisms may dictate the localization and activity of the protein during differentiation. Presented by: Leondaritis, George Poster No 062 Green Session 144
Cell Biology of the Neuron: <strong>Polarity</strong>, Plasticity and Regeneration, Crete 2011 Development of the Corticospinal Tract: Integration into Spinal Circuitry Important for Coordinating Complex Motor Behaviors Kathryn Lewallen, Ariel Levine, Sam Pfaff Salk Institute The corticospinal tract (CST) forms the longest axon trajectory in the mammalian central nervous system, extending processes from the motor cortex to functional targets throughout the length of the spinal cord. As a graduate student in the laboratory of Dr. Sam Pfaff at the Salk Institute, I am interested in understanding how corticospinal motor neurons integrate intrinsic and extrinsic cues to carry out specified functions, such as coordinating complex motor behaviors. Specifically, my thesis project involves the identification of cellular players and molecules that direct synaptic specificity during development. I am using novel genetic tools combined with single axon fiber resolution to study the CST during axonal growth, synaptic target selection, and activity-dependent maturation. My analysis includes a comprehensive descriptive analysis of the CST in normal development and in mutants that perturb CST formation and axon guidance. By understanding the mechanisms that direct corticospinal connectivity, we can gain additional insight into the pathways that can be recapitulated in a regenerative context. Presented by: Lewallen, Kathryn 145 Poster No 063 Blue Session
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The meeting was funded in part by E
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These abstracts should not be cited
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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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Cell Biology of the Neuron: Polarit
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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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Dr. Med. Andreas Vlachos Goethe‐U
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