Neuroscience 2003 Abstract
| Presentation Number: | 34.16 |
|---|---|
| Abstract Title: | BDNF regulates filopodial dynamics through ADF/cofilin. |
| Authors: |
Gehler, S.*1
; Bamburg, J.2
; Letourneau, P. C.1
1Dept. of Neurosci., Univ. of Minnesota, Minneapolis, MN 2CO, 6-145 Jackson Hall, 55455, |
| Primary Theme and Topics |
Development - Axonal and Dendritic Development -- Axon growth and guidance: receptors and signaling mechanisms |
| Session: |
34. Axon Growth and Guidance: Receptors and Signaling Mechanisms--Intracellular Signaling Poster |
| Presentation Time: | Saturday, November 8, 2003 4:00 PM-5:00 PM |
| Location: | Morial Convention Center - Hall F-I, Board # B44 |
| Keywords: | growth cone, neurotrophin, actin, Rho |
Growth cone guidance involves changes in growth cone behaviors mediated by environmental signals. Although it is well appreciated that growth cone filopodia are important in detection and response to guidance cues, mechanisms by which guidance cues regulate filopodial dynamics are not understood. Neurotrophins regulate growth cone morphology, but the signaling mechanisms involved are complex and not fully understood. Our evidence suggests that BDNF modulates filopodial dynamics by regulating actin depolymerization through ADF/cofilin. First, BDNF causes a 34% increase in filopodial length on chick retinal ganglion cell (RGC) growth cones. We have shown that BDNF-induced increases in filopodial length are mediated through a RhoA pathway (SFN abstract, 2002). Second, inhibition of Rho kinase (ROCK) with Y-27632 causes a 34% increase in filopodial length, mimicking the effects of BDNF. Further, addition of BDNF to Y-27632-treated cultures has no additional effect on filopodial length. To determine the role of ADF/cofilin in BDNF-induced increases on filopodial length, we used a lipid-based protein loading reagent (ChariotTM, Active Motif) to test the effects of constitutively-active or minimally-active ADF/cofilin on RGC growth cones. Constitutively-active ADF/cofilin [XAC(3A)] causes a 30% increase in filopodial length, and BDNF has no further effect. Conversely, minimally-active ADF/cofilin [XAC(3E)] has no effect on filopodial length, but blocks the lengthening effects of BDNF. Therefore, XAC(3E) has a dominant-negative effect on BDNF-induced increases in filopodial length. Furthermore, we show that phosphorylation levels of ADF/cofilin are regulated by BDNF. These data suggest that BDNF signals through ADF/cofilin to regulate actin dynamics and filopodial length.
Supported by NIH HD19950 (PCL), GM35126 (JB), NSF IBN0080932 (PCL), and EYO7133 (SG)
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2003 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2003. Online.
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