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

Bryan W Luikart; Wei Zhang; Gary A Wayman; Chang-Hyuk Kwon; Gary L Westbrook; Luis F Parada

doi:10.1523/JNEUROSCI.0195-08.2008

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

Journal article

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

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

The Journal of neuroscience, Vol.28(27), pp.7006-7012

07/02/2008

DOI: https://doi.org/10.1523/JNEUROSCI.0195-08.2008

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https://hdl.handle.net/2376/112707

PMCID: PMC3397478

PMID: 18596174

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Abstract

Phosphatidylinositol Phosphates - metabolism

Pseudopodia - ultrastructure

Dendrites - ultrastructure

Phosphatidylinositol 3-Kinases - metabolism

Cell Movement - physiology

Pseudopodia - drug effects

Brain-Derived Neurotrophic Factor - pharmacology

Synapses - metabolism

Brain-Derived Neurotrophic Factor - metabolism

Receptor, trkB - drug effects

Hippocampus - growth & development

Organ Culture Techniques

Animals, Newborn

Dendrites - drug effects

Dendrites - metabolism

PTEN Phosphohydrolase - genetics

Synapses - drug effects

Cells, Cultured

Rats

Synapses - ultrastructure

Hippocampus - cytology

Rats, Sprague-Dawley

Mice, Knockout

Cell Movement - drug effects

Hippocampus - metabolism

Animals

Growth Cones - metabolism

Growth Cones - ultrastructure

Pseudopodia - metabolism

Signal Transduction - drug effects

Signal Transduction - physiology

Mice

Growth Cones - drug effects

Neurofibromin 1 - genetics

Receptor, trkB - metabolism

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.

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Title: Neurotrophin-dependent dendritic filopodial motility: a convergence on PI3K signaling
Creators: Bryan W Luikart - 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
Wei Zhang
Gary A Wayman
Chang-Hyuk Kwon
Gary L Westbrook
Luis F Parada
Publication Details: The Journal of neuroscience, Vol.28(27), pp.7006-7012
Academic Unit: Department of Integrative Physiology and Neuroscience
Publisher: United States
Grant note: R01 MH046613 / NIMH NIH HHS P50 NS 052606 / NINDS NIH HHS R37 NS033199 / NINDS NIH HHS R37 MH046613 / NIMH NIH HHS F32 MH079548 / NIMH NIH HHS R37NS33199 / NINDS NIH HHS P50 NS052606-04 / NINDS NIH HHS F32MH079548 / NIMH NIH HHS MH46613 / NIMH NIH HHS P50 NS052606 / NINDS NIH HHS
Identifiers: 99900548096901842
Language: English
Resource Type: Journal article