Neuroscience 2004 Abstract
| Presentation Number: | 723.15 |
|---|---|
| Abstract Title: | NGF and integrin signaling pathways converge to mediate embryonic axon elongation. |
| Authors: |
Walzer, M. A.*1
; Zhou, F.1
; Wu, Y.1
; Dedhar, S.2
; Snider, W. D.1
1Dept Neurosci., Univ. of North Carolina, Chapel Hill, NC 2BC, 103 Mason Farm Rd, 27599, |
| Primary Theme and Topics |
Development - Axonal and Dendritic Development -- Axon growth and guidance: receptors and signaling mechanisms |
| Secondary Theme and Topics | Development<br />- Axonal and Dendritic Development<br />-- Axon growth and guidance: extracellular signals |
| Session: |
723. Axon Guidance III Poster |
| Presentation Time: | Tuesday, October 26, 2004 3:00 PM-4:00 PM |
| Location: | San Diego Convention Center - Hall A-H, Board # D20 |
| Keywords: | Integrin-linked kinase, GSK-3beta, PKC, Polarity |
Coordinated activation of integrin and growth factor signaling is necessary for efficient axon elongation induced by NGF. However, exactly where neurotrophin and integrin signaling pathways intersect in the mediation of axon growth is not known. Our work and the work of others have shown that inhibition of integrin-linked kinase (ILK), a β1 and β3 integrin subunit bound serine/threonine kinase, blocks NGF-induced axon growth on laminin by reducing GSK-3β phosphorylation (Mills et al., J. Neurosci. 23(5): 1638-48, 2003; Zhou et al. Neuron, in press). We show here that embryonic dorsal root ganglion (DRG) neurons plated on polylysine in the absence of integrin activation also show reduced GSK-3β phosphorylation and decreased axon growth in response to NGF compared to embryonic DRG neurons plated on laminin. Together these data suggest that integrin and NGF signaling may converge through ILK to regulate GSK-3β activity and axon growth. Furthermore, by using a variety of kinase inhibitors, we have identified atypical PKCs (PKC ζ/λ) as key regulators of GSK-3β phosphorylation in embryonic DRG neurons. Finally, ILK inhibition significantly reduced the activation of PKC ζ/λ, indicating that ILK acts in this pathway upstream of PKC ζ/λ. Taken together, our results suggest that integrin and NGF signaling converge on ILK to regulate embryonic DRG axon elongation via modulation of PKC ζ/λ and GSK-3β activity.
Supported by NIH NS031768 to W.D.S. and fellowship from the SCRF to F-Q.Z.
<B>Conflict of Interest:</B> Shoukat Dedhar has a financial interest in Kinetek Pharmaceuticals (now owned by QLT Inc.) which provided the ILK inhibitor KP-074728.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2004 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2004. Online.
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