Neuroscience 2002 Abstract
| Presentation Number: | 528.14 |
|---|---|
| Abstract Title: | AN-1, a neuronal RhoGAP homologue involved in NGF-stimulated axon growth. |
| Authors: |
Zhong, J.*1
; Markus, A.1
; Wennerberg, K.2
; Patterson, P. H.3
; Snider, W. D.1
1Neuroscience Center, University of North Carolina, Chapel Hill, NC 2Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 3Division of Biology, California Institute of Technology, Pasadena, CA |
| Primary Theme and Topics |
Development - Axonal and Dendritic Development -- Axon growth and guidance: receptors and signaling mechanisms |
| Session: |
528. Axonal and dendritic development: axon growth and guidance--receptors and signaling mechanisms I Poster |
| Presentation Time: | Tuesday, November 5, 2002 2:00 PM-3:00 PM |
| Location: | Hall A2-B3 B-20 |
| Keywords: | subtractive cloning, TRANSFECTION, SIGNAL TRANSDUCTION, DORSAL ROOT GANGLION |
Attempting to clone genes involved in nerve growth factor (NGF)-induced neurite extension, we cultured dorsal root ganglion (DRG) explants with either NGF or NT3. Using subtraction methods, cDNAs expressed exclusively in NGF-treated explants were enriched, cloned and sequenced. We identified several known genes, and we also found more than 100 novel gene fragments. One of these, designated AN-1, has stretches of significant homology to the GTPase-activating protein RhoGAP. RhoGAP participates in the control of the Rho family small G-proteins, which have been shown to regulate the actin cytoskeleton as well as neurite outgrowth. A search of EST databases and RT-PCR analysis suggest that at least 13 further homologues of AN-1 exist. We found that immunoprecipitation of AN-1 co-precipitates active RhoA, but not RhoG, Rac or Cdc42. Deletion of the RhoGAP domain in AN-1 eliminates this binding. In situ hybridization shows AN-1 mRNA selectively and highly expressed in embryonic DRG and sympathetic neurons as well as a subset of spinal motor neurons. Expression in the DRG is highest at embryonic day E11, when sensory axons begin to extend towards the periphery. This suggests that AN-1 may be involved in sensory axon outgrowth. In perturbation studies, overexpression of AN-1 in PC12 cells induces neurite outgrowth. Furthermore, in cultured E13.5 DRG neurons, expression of AN1Δ, a derivative of AN-1 with its RhoGAP domain deleted, inhibits NGF-induced axon outgrowth. We conclude that AN-1 participates in NGF-induced neurite growth through regulation of RhoA.
Supported by NS31768
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2002 Neuroscience Meeting Planner. Orlando, FL: Society for Neuroscience, 2002. Online.
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