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

More documents

Recommendations

Info

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
Page 1:
Abstracts of papers presented at th
Page 4 and 5:
The meeting was funded in part by E
Page 6 and 7:
These abstracts should not be cited
Page 8 and 9:
CYFIP1, a Neuronal eIF4E‐BP, Link
Page 10 and 11:
POSTER ABSTRACTS Poster # [‐R(ed)
Page 12 and 13:
030‐B Paracrine Pax6 Activity Reg
Page 14 and 15:
058‐R Dynein Light Chain LC8 is a
Page 16 and 17:
088‐R Spectraplakins ‐ Cytoskel
Page 18 and 19:
121‐R Calmyrin1 Binds to SCG10 Pr
Page 20 and 21:
18.00 ‐ 18.15 Non Hyperpolarizing
Page 22 and 23:
10.00 ‐ 10.30 Neurotrophin Regula
Page 24 and 25:
SESSION 10 SYNAPTOGENESIS Chairpers
Page 26 and 27:
da F. Costa, L. 119 D'Adamo, P. 108
Page 28 and 29:
Lewallen, K. 145 Li, Y.‐H. 201 Li
Page 30 and 31:
Teuling, E. 141 Thiebes, K. 87 Thom
Page 33 and 34:
Cell Biology of the Neuron: Polarit
Page 35 and 36:
Page 37 and 38:
Page 39 and 40:
Page 41 and 42:
Page 43 and 44:
Page 45 and 46:
Page 47 and 48:
Page 49 and 50:
Page 51 and 52:
Page 53 and 54:
Page 55 and 56:
Page 57 and 58:
Page 59 and 60:
Page 61 and 62:
Page 63 and 64:
Page 65 and 66:
Page 67 and 68:
Page 69 and 70:
Page 71 and 72:
Page 73 and 74:
Page 75 and 76:
Page 77 and 78:
Page 79:
Page 83 and 84:
Page 85 and 86:
Page 87 and 88:
Page 89 and 90:
Page 91 and 92:
Page 93 and 94:
Page 95 and 96:
Page 97 and 98:
Page 99 and 100:
Page 101 and 102:
Page 103 and 104:
Page 105 and 106:
Page 107 and 108:
Page 109 and 110:
Page 111 and 112:
Page 113 and 114:
Page 115 and 116:
Page 117 and 118:
Page 119 and 120:
Page 121 and 122:
Page 123 and 124:
Page 125 and 126: Cell Biology of the Neuron: Polarit
Page 175: Cell Biology of the Neuron: Polarit
Page 209 and 210: Dr. Christian Alfano INSERM U636, N
Page 211 and 212: Prof. Graeme W. Davis University of
Page 213 and 214: Prof. Zhigang He Harvard Medical Sc
Page 215 and 216: Dr. Bernhard Lohkamp Karolinska Ins
Page 217 and 218: Mr. Abhishek Shrikant Sahasrabudhe
Page 219: Dr. Med. Andreas Vlachos Goethe‐U
Page 226 and 227:
NOTES:
Page 228 and 229:
NOTES:
Page 230:
NOTES:
show all

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

Create successful ePaper yourself

Delete template?

Save as template?