PMID- 18596174
OWN - NLM
STAT- MEDLINE
DCOM- 20080812
LR  - 20211020
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 28
IP  - 27
DP  - 2008 Jul 2
TI  - Neurotrophin-dependent dendritic filopodial motility: a convergence on PI3K 
      signaling.
PG  - 7006-12
LID - 10.1523/JNEUROSCI.0195-08.2008 [doi]
AB  - 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.
FAU - Luikart, Bryan W
AU  - Luikart BW
AD  - Department of Developmental Biology and Kent Waldrep Foundation Center for 
      Research on Nerve Growth and Regeneration, University of Texas Southwestern 
      Medical School, Dallas, Texas 75390-9133, USA.
FAU - Zhang, Wei
AU  - Zhang W
FAU - Wayman, Gary A
AU  - Wayman GA
FAU - Kwon, Chang-Hyuk
AU  - Kwon CH
FAU - Westbrook, Gary L
AU  - Westbrook GL
FAU - Parada, Luis F
AU  - Parada LF
LA  - eng
GR  - MH46613/MH/NIMH NIH HHS/United States
GR  - R01 MH046613/MH/NIMH NIH HHS/United States
GR  - F32 MH079548/MH/NIMH NIH HHS/United States
GR  - P50 NS052606-04/NS/NINDS NIH HHS/United States
GR  - R37NS33199/NS/NINDS NIH HHS/United States
GR  - P50 NS 052606/NS/NINDS NIH HHS/United States
GR  - R37 NS033199/NS/NINDS NIH HHS/United States
GR  - P50 NS052606/NS/NINDS NIH HHS/United States
GR  - F32MH079548/MH/NIMH NIH HHS/United States
GR  - R37 MH046613/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neurofibromin 1)
RN  - 0 (Phosphatidylinositol Phosphates)
RN  - 0 (phosphatidylinositol 3,4,5-triphosphate)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (Pten protein, mouse)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Brain-Derived Neurotrophic Factor/*metabolism/pharmacology
MH  - Cell Movement/drug effects/physiology
MH  - Cells, Cultured
MH  - Dendrites/drug effects/*metabolism/ultrastructure
MH  - Growth Cones/drug effects/metabolism/ultrastructure
MH  - Hippocampus/cytology/*growth & development/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Neurofibromin 1/genetics
MH  - Organ Culture Techniques
MH  - PTEN Phosphohydrolase/genetics
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphatidylinositol Phosphates/metabolism
MH  - Pseudopodia/drug effects/*metabolism/ultrastructure
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/drug effects/metabolism
MH  - Signal Transduction/drug effects/physiology
MH  - Synapses/drug effects/metabolism/ultrastructure
PMC - PMC3397478
MID - NIHMS320795
EDAT- 2008/07/04 09:00
MHDA- 2008/08/13 09:00
PMCR- 2009/01/02
CRDT- 2008/07/04 09:00
PHST- 2008/07/04 09:00 [pubmed]
PHST- 2008/08/13 09:00 [medline]
PHST- 2008/07/04 09:00 [entrez]
PHST- 2009/01/02 00:00 [pmc-release]
AID - 28/27/7006 [pii]
AID - 3370264 [pii]
AID - 10.1523/JNEUROSCI.0195-08.2008 [doi]
PST - ppublish
SO  - J Neurosci. 2008 Jul 2;28(27):7006-12. doi: 10.1523/JNEUROSCI.0195-08.2008.