Neurotrophin-dependent dendritic filopodial motility: A convergence on PI3K signaling

Bryan W. Luikart, Wei Zhang, Gary A. Wayman, Chang Hyuk Kwon, Gary Westbrook, Luis F. Parada

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Synapse formation requires contact between dendrites and axons. Although this process is often viewed as axon mediated, dendritic filopodia may be actively involved in mediating synaptogenic contact. Although the signaling cues underlying dendritic filopodial motility are mostly unknown, brain-derived neurotrophic factor (BDNF) increases the density of dendritic filopodia and conditional deletion of tyrosine receptor kinase B (TrkB) reduces synapse number in vivo. Here, we report that TrkB associates with dendritic growth cones and filopodia, mediates filopodial motility, and does so via the phosphoinositide 3 kinase (PI3K) pathway. We used genetic and pharmacological manipulations of mouse hippocampal neurons to assess signaling downstream of TrkB. Conditional knock-out of two downstream negative regulators of TrkB signaling, Pten (phosphatase with tensin homolog) and Nf1 (neurofibromatosis type 1), enhanced filopodial motility. This effect was PI3K-dependent and correlated with synaptic density. Phosphatidylinositol 3,4,5-trisphosphate (PIP3) was preferentially localized in filopodia and this distribution was enhanced by BDNF application. Thus, intracellular control of filopodial dynamics converged on PI3K activation and PIP3 accumulation, a cellular paradigm conserved for chemotaxis in other cell types. Our results suggest that filopodial movement is not random, but responsive to synaptic guidance molecules.

Original languageEnglish (US)
Pages (from-to)7006-7012
Number of pages7
JournalJournal of Neuroscience
Volume28
Issue number27
DOIs
StatePublished - Jul 2 2008

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Pseudopodia
1-Phosphatidylinositol 4-Kinase
Nerve Growth Factors
Receptor Protein-Tyrosine Kinases
Brain-Derived Neurotrophic Factor
Synapses
Axons
Growth Cones
Neurofibromatosis 1
Chemotaxis
Dendrites
Phosphoric Monoester Hydrolases
Cues
Pharmacology
Neurons

Keywords

  • BDNF
  • Filopodia
  • PIP2
  • PIP3
  • Spine
  • TrkB

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

Neurotrophin-dependent dendritic filopodial motility : A convergence on PI3K signaling. / Luikart, Bryan W.; Zhang, Wei; Wayman, Gary A.; Kwon, Chang Hyuk; Westbrook, Gary; Parada, Luis F.

In: Journal of Neuroscience, Vol. 28, No. 27, 02.07.2008, p. 7006-7012.

Research output: Contribution to journalArticle

Luikart, Bryan W. ; Zhang, Wei ; Wayman, Gary A. ; Kwon, Chang Hyuk ; Westbrook, Gary ; Parada, Luis F. / Neurotrophin-dependent dendritic filopodial motility : A convergence on PI3K signaling. In: Journal of Neuroscience. 2008 ; Vol. 28, No. 27. pp. 7006-7012.
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