Brain-derived neurotrophic factor regulation of retinal growth cone filopodial dynamics is mediated through actin depolymerizing factor/cofilin.
The molecular mechanisms by which neurotrophins regulate growth cone motility are not well understood. This study investigated the signaling involved in transducing BDNF-induced increases of filopodial dynamics. Our results indicate that BDNF regulates filopodial length and number through a Rho kinase-dependent mechanism. Additionally, actin depolymerizing factor (ADF)/cofilin activity is necessary and sufficient to transduce the effects of BDNF. Our data indicate that activation of ADF/cofilin mimics the effects of BDNF on filopodial dynamics, whereas ADF/cofilin inactivity blocks the effects of BDNF. Furthermore, BDNF promotes the activation of ADF/cofilin by reducing the phosphorylation of ADF/cofilin. Although inhibition of myosin II also enhances filopodial length, our results indicate that BDNF signaling is independent of myosin II activity and that the two pathways result in additive effects on filopodial length. Thus, filopodial extension is regulated by at least two independent mechanisms. The BDNF-dependent pathway works via regulation of ADF/cofilin, independently of myosin II activity.
Gehler
Scott
S
Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Shaw
Alisa E
AE
Sarmiere
Patrick D
PD
Bamburg
James R
JR
Letourneau
Paul C
PC
D048948:14-3-3 Proteins / Q000502:physiology; D051339:Actin Depolymerizing Factors; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D002642:Chick Embryo; D051345:Destrin; D020439:Growth Cones / Q000502:physiology* / Q000648:ultrastructure; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins / Q000378:metabolism / Q000502:physiology*; D024462:Myosin Type II / Q000037:antagonists & inhibitors / Q000502:physiology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D011554:Pseudopodia / Q000502:physiology*; D012160:Retina / Q000648:ultrastructure*; D015398:Signal Transduction / Q000502:physiology; D046509:Tissue Culture Techniques; D054460:rho-Associated Kinases
D048948:14-3-3 Proteins; D051339:Actin Depolymerizing Factors; D019208:Brain-Derived Neurotrophic Factor; D051345:Destrin; D006576:Heterocyclic Compounds, 4 or More Rings; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; C472645:blebbistatin; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D024462:Myosin Type II