IHEM   20887
INSTITUTO DE HISTOLOGIA Y EMBRIOLOGIA DE MENDOZA DR. MARIO H. BURGOS
Unidad Ejecutora - UE
artículos
Título:
The neuronal Arf GAP centaurin alpha1 modulates dendritic differentiation
Autor/es:
MOORE, CD; THACKER, EE; LARIMORE, J; GASTON, D; UNDERWOOD, A; KEARNS, B; PATTERSON, SI; JACKSON, T; CHAPLEAU, C; POZZO-MILLER, L; THEIBERT, A
Revista:
JOURNAL OF CELL SCIENCE
Referencias:
Año: 2007 vol. 120 p. 2683 - 2693
ISSN:
0021-9533
Resumen:
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 GAPdependent
Arf regulation of dendritic branching and
spines that underlie normal dendritic differentiation and
development.