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Cell Biology of the Neuron: <strong>Polarity</strong>, Plasticity and Regeneration, Crete 2011 Effects of Microtubule Stabilization on Axon Regeneration in Clinically Relevant Approaches Jörg Ruschel 1 , Andres Hurtado 2 , Farida Hellal 1 , Vance Lemmon 3 , John Bixby 3 1 , Frank Bradke 1 Max-Planck-Institute of Neurobiology,Martinsried,Germany 2 Hugo Moser Research Institute at Kennedy-Krieger, Johns-Hopkins University, Baltimore, USA 3 Miami Project to cure paralysis, Miller school of medicine, University of Miami Microtubule stabilization promotes regeneration of injured spinal cord axons by increasing intrinsic neuronal growth capacity and removing extrinsic inhibitory factors. Here we aimed to demonstrate the benefit of the microtubule stabilizing drug Taxol for spinal cord regeneration and functional recovery in a clinically relevant injury model. After contusion injury, Taxol treatment decreases fibrotic scarring and stimulates axonal regeneration resulting in a significant improvement of finetuned locomotion. In addition, we tested a new class of microtubule stabilizing agents, the Epothilones which are, in contrast to Taxol, crossing the Blood Brain Barrier and without pro-inflammatory side effects. In vitro, Epothilone-B increases axonal growth competence enabling cultured neurons to overcome growth inhibitory substrates. Moreover, in vivo live-imaging studies revealed that Epothilone-B treatment reduces dystrophic-endbulb formation of cut dorsal column axons. Additionally, Epothilone-B inhibits fibrotic scarring and increases axonal regeneration after spinal cord hemisection in rats. Taken together these results emphasize the clinical relevance of microtubule stabilization to stimulate axonal regeneration in the injured central nervous Presented by: Ruschel, Jörg Poster No 094 Red Session 176
Cell Biology of the Neuron: <strong>Polarity</strong>, Plasticity and Regeneration, Crete 2011 Cell-Contact Induced Eph Receptor Trans- Endocytosis Activates an SFK Dependent Phagocytic Pathway Maria Sakkou, Rüdiger Klein Max Planck Institute of Neurobiology, Department of Molecular Neurobiology, Martinsried, Germany Cells have self-organizing features that control their behavior in complex tissues. Ephrins are membrane tethered guidance cues that bind to Eph receptor tyrosine kinases (RTKs). During development the Eph/ephrin signaling system controls a large variety of cellular responses including contact-mediated attraction or repulsion, adhesion or de-adhesion and migration. Moreover, unlike other RTKs, Eph/ephrin signaling dynamics are regulated by a large number of components like proteolytic cleavage, trans-endocytosis, bi-directional signaling, higher order clustering and cis-interactions of Ephs and ephrins. Their relative contribution though during brain development is not yet known. Ongoing work indicates that bidirectional endocytosis is a critical regulator of growth cone collapse and in cell culture is required to convert an otherwise adhesive force provided by the interaction of the receptors and ligands to a repulsive signal. My aims are to study the role of endocytosis in Eph/ephrin signaling, to characterize the endocytic pathways that are activated by Ephs and ephrins and to investigate their relative functional role. In a candidate approach we undertook we found that although Src family kinases (SFKs) are phosphorylated and activated downstream of both Eph receptor and ephrin ligand they are required for ephrin “reverse”, but not Eph “forward” trans- endocytosis. Furthermore, we show that Src requirement is exclusive for cell-cell interaction but not for soluble ligand stimulation and that trafficking of Eph/ephrin complexes require Rab5 activation, actin cytoskeleton polymerization and PI3K activation. To further assess the functional role of endocytosis we blocked SFK activation in primary neurons and observed that deattachment between ephrinB growth cones and EphB2 cells was significantly slower. Taken together these data indicate that Eph/ephrin complexes are internalized via a phagocytic –like mechanism and that downstream of ephrin SFKs activate a novel pathway independent of the phosphotyrosine and PDZ dependent signaling networks that is required for receptor internalization and cell de-attachment. Presented by: Sakkou, Maria 177 Poster No 095 Green 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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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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