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The neuronal Arf GAP centaurin α1 modulates dendritic differentiation

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Moore, Carlene D., Thacker, Erin E., Larimore, Jennifer, Gaston, David, Underwood, Alison, Kearns, Brian, Patterson, Sean I., Jackson, Trevor +3 more·2007·Journal of Cell Science
DOI 10.1242/jcs.006346PMC PMC2810648
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Abstract

Centaurin α1 is an Arf GTPase-activating protein (GAP) that is highly expressed in the nervous system. In the current study, we show that endogenous centaurin α1 protein is localized in the synaptosome fraction, with peak expression in early postnatal development. In cultured dissociated hippocampal neurons, centaurin α1 localizes to dendrites, dendritic spines and the postsynaptic region. siRNA-mediated knockdown of centaurin α1 levels or overexpression of a GAP-inactive mutant of centaurin α1 leads to inhibition of dendritic branching, dendritic filopodia and spine-like protrusions in dissociated hippocampal neurons. Overexpression of wild-type centaurin α1 in cultured hippocampal neurons in early development enhances dendritic branching, and increases dendritic filopodia and lamellipodia. Both filopodia and lamellipodia have been implicated in dendritic branching and spine formation. Following synaptogenesis in cultured neurons, wild-type centaurin α1 expression increases dendritic filopodia and spine-like protrusions. Expression of a GAP-inactive mutant diminishes spine density in CA1 pyramidal neurons within cultured organotypic hippocampal slice cultures. These data support the conclusion that centaurin α1 functions through GAP-dependent Arf regulation of dendritic branching and spines that underlie normal dendritic differentiation and development.

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  • Members of the ARF family of small GTPases and their regulators are important regulators of spine density and morphology.

    “Members of the ADP-ribosylation factor (ARF) family of small GTPases and their regulators have gained increasing attention as important regulators of spine density and morphology [27], [28], [29].”

    From Arf4 Determines Dentate Gyrus-Mediated Pattern Separation by Regulating Dendritic Spine Development (2012) · cites this paper as [29]

  • Overexpression of GFP-β-actin does not impair neuronal function or dendritic spine morphology and density.

    “Overexpression of GFP-β-actin does not impair neuronal function or dendritic spine morphology and density and can, therefore, be used to highlight dendritic spines for imaging and quantification [29], [45].”

    From Arf4 Determines Dentate Gyrus-Mediated Pattern Separation by Regulating Dendritic Spine Development (2012) · cites this paper as [29]

    The Materials and Methods describe using eYFP to visualize dendrites and spines, not GFP-β-actin. The Results compare spine density after centaurin α1 expression, but do not assess whether GFP-β-actin overexpression affects neuronal function or spine morphology and density. Searches for GFP-β-actin and GFP-actin found no passage addressing that claim; page numbers were unavailable in our copy. (LLM, conf=0.76)

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Moore, C. D., Thacker, E. E., Larimore, J., Gaston, D., Underwood, A., Kearns, B., Patterson, S. I., Jackson, T., Chapleau, C., Pozzo-Miller, L., & Theibert, A.
Affiliations
  • Civitan International (US)
  • Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
  • Newcastle University (GB)
  • Department of Neurobiology and Civitan International Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Corresponding author
Theibert, Anne
ORCID
Venue
Journal of Cell Science
Publisher
The Company of Biologists
Published
2007-08-01
Volume
120
Issue
15
Pages
2683-2693
ISSN
  • 0021-9533 (ISSN-L)
  • 1477-9137
DOI
10.1242/jcs.006346
PMC
PMC2810648
OpenAlex
W2072446626
Cited by
40
References
3
Citations by year
2025: 3 · 2024: 1 · 2023: 1 · 2021: 1 · 2020: 5 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 3 · 2014: 3 · 2013: 3 · 2012: 3
FWCI
1.25
Type
journal article
Language
en
Open access
Locations
  • Journal of Cell Science (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Newcastle University ePrints (Newcastle Univesity)
Funders
  • National Institute of Mental Health (R01MH050102, MH50102, R29MH050102)
  • National Institute of Neurological Disorders and Stroke (R01NS040593)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
Arf GTPase-activating protein, dendritic differentiation, dendritic branching, dendritic spines, dendritic filopodia, lamellipodia, hippocampal neurons, synaptogenesis, CA1 pyramidal neurons, postnatal development, synaptosomes
MeSH terms
Animals, Brain, Cell Differentiation, Cells, Cultured, Cytoskeletal Proteins, Dendrites, Hippocampus, Nerve Tissue Proteins, Neurons, Synapses, GTPase-Activating Proteins, RNA, Small Interfering, Adaptor Proteins, Signal Transducing, Rats

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