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The neuronal Arf GAP centaurin α1 modulates dendritic differentiation

Lookup NU author(s): Dr Trevor Jackson

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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.


Publication metadata

Author(s): Moore CD, Thacker EE, Larimore J, Gaston D, Underwood A, Kearns B, Patterson SI, Jackson T, Chapleau C, Pozzo-Miller L, Theibert A

Publication type: Article

Publication status: Published

Journal: Journal of Cell Science

Year: 2007

Volume: 120

Issue: 15

Pages: 2683-2693

ISSN (print): 0021-9533

ISSN (electronic): 1477-9137

Publisher: The Company of Biologists Ltd.

URL: http://dx.doi.org/10.1242/jcs.006346

DOI: 10.1242/jcs.006346

PubMed id: 17635995


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