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Preso, a novel PSD-95-interacting FERM and PDZ domain protein that regulates dendritic spine morphogenesis.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2008 Dec 31; Vol. 28 (53), pp. 14546-56. - Publication Year :
- 2008
-
Abstract
- PSD-95 is an abundant postsynaptic density (PSD) protein involved in the formation and regulation of excitatory synapses and dendritic spines, but the underlying mechanisms are not comprehensively understood. Here we report a novel PSD-95-interacting protein Preso that regulates spine morphogenesis. Preso is mainly expressed in the brain and contains WW (domain with two conserved Trp residues), PDZ (PSD-95/Dlg/ZO-1), FERM (4.1, ezrin, radixin, and moesin), and C-terminal PDZ-binding domains. These domains associate with actin filaments, the Rac1/Cdc42 guanine nucleotide exchange factor betaPix, phosphatidylinositol-4,5-bisphosphate, and the postsynaptic scaffolding protein PSD-95, respectively. Preso overexpression increases the density of dendritic spines in a manner requiring WW, PDZ, FERM, and PDZ-binding domains. Conversely, knockdown or dominant-negative inhibition of Preso decreases spine density, excitatory synaptic transmission, and the spine level of filamentous actin. These results suggest that Preso positively regulates spine density through its interaction with the synaptic plasma membrane, actin filaments, PSD-95, and the betaPix-based Rac1 signaling pathway.
- Subjects :
- Actin Cytoskeleton metabolism
Animals
Cells, Cultured
Chlorocebus aethiops
Cricetinae
Disks Large Homolog 4 Protein
Embryo, Mammalian
Gene Expression physiology
Green Fluorescent Proteins genetics
Green Fluorescent Proteins metabolism
Guanylate Kinases
Hippocampus cytology
Humans
Intracellular Signaling Peptides and Proteins genetics
Intracellular Signaling Peptides and Proteins metabolism
Membrane Proteins metabolism
Microtubule-Associated Proteins metabolism
Models, Molecular
Morphogenesis physiology
Nerve Tissue Proteins metabolism
Phosphatidylinositol 4,5-Diphosphate metabolism
Protein Structure, Tertiary
Rats
Synaptic Transmission genetics
Transfection
Two-Hybrid System Techniques
Cytoskeletal Proteins physiology
Dendritic Spines physiology
Intracellular Signaling Peptides and Proteins physiology
Neurons ultrastructure
PDZ Domains physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 28
- Issue :
- 53
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 19118189
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.3112-08.2008