The neuronal Arf GAP centaurin alpha1 modulates dendritic differentiation.
Centaurin alpha1 is an Arf GTPase-activating protein (GAP) that is highly expressed in the nervous system. In the current study, we show that endogenous centaurin alpha1 protein is localized in the synaptosome fraction, with peak expression in early postnatal development. In cultured dissociated hippocampal neurons, centaurin alpha1 localizes to dendrites, dendritic spines and the postsynaptic region. siRNA-mediated knockdown of centaurin alpha1 levels or overexpression of a GAP-inactive mutant of centaurin alpha1 leads to inhibition of dendritic branching, dendritic filopodia and spine-like protrusions in dissociated hippocampal neurons. Overexpression of wild-type centaurin alpha1 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 alpha1 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 alpha1 functions through GAP-dependent Arf regulation of dendritic branching and spines that underlie normal dendritic differentiation and development.
Moore
Carlene D
CD
Department of Neurobiology and Civitan International Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Thacker
Erin E
EE
Larimore
Jennifer
J
Gaston
David
D
Underwood
Alison
A
Kearns
Brian
B
Patterson
Sean I
SI
Jackson
Trevor
T
Chapleau
Chris
C
Pozzo-Miller
Lucas
L
Theibert
Anne
A
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000302:isolation & purification / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure*; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D034741:RNA, Small Interfering; D051381:Rats; D013569:Synapses
C491062:Adap1 protein, rat; D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D020690:GTPase-Activating Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering