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 βPix, 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 βPix-based Rac1 signaling pathway.
| Original language | English |
|---|---|
| Pages (from-to) | 14546-14556 |
| Number of pages | 11 |
| Journal | Journal of Neuroscience |
| Volume | 28 |
| Issue number | 53 |
| DOIs | |
| Publication status | Published - 2008 Dec 31 |
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Keywords
- Actin
- FERM
- PDZ
- PSD-95
- Spine
- WW
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Preso, a novel PSD-95-interacting FERM and PDZ domain protein that regulates dendritic spine morphogenesis. / Hyun, Woo Lee; Choi, Jeonghoon; Shin, Hyewon; Kim, Karam; Yang, Jinhee; Na, Moonseok; So, Yoen Choi; Gil, Bu Kang; Soo, Hyun Eom; Kim, Hyun; Kim, Eunjoon.
In: Journal of Neuroscience, Vol. 28, No. 53, 31.12.2008, p. 14546-14556.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Preso, a novel PSD-95-interacting FERM and PDZ domain protein that regulates dendritic spine morphogenesis
AU - Hyun, Woo Lee
AU - Choi, Jeonghoon
AU - Shin, Hyewon
AU - Kim, Karam
AU - Yang, Jinhee
AU - Na, Moonseok
AU - So, Yoen Choi
AU - Gil, Bu Kang
AU - Soo, Hyun Eom
AU - Kim, Hyun
AU - Kim, Eunjoon
PY - 2008/12/31
Y1 - 2008/12/31
N2 - 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 βPix, 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 βPix-based Rac1 signaling pathway.
AB - 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 βPix, 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 βPix-based Rac1 signaling pathway.
KW - Actin
KW - FERM
KW - PDZ
KW - PSD-95
KW - Spine
KW - WW
UR - http://www.scopus.com/inward/record.url?scp=58149392098&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=58149392098&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.3112-08.2008
DO - 10.1523/JNEUROSCI.3112-08.2008
M3 - Article
C2 - 19118189
AN - SCOPUS:58149392098
VL - 28
SP - 14546
EP - 14556
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 53
ER -