Synaptic targeting of PSD-Zip45 (Homer 1c) and its involvement in the synaptic accumulation of F-actin.
PSD-Zip45/Homer1c, which contains an enabled/VASP homology 1 (EVH1) domain and leucine zipper motifs, is a postsynaptic density (PSD) scaffold protein that interacts with metabotropic glutamate receptors and the shank family. We studied the molecular mechanism underlying the synaptic targeting of PSD-Zip45 in cultured hippocampal neurons. The EVH1 domain and the extreme C-terminal leucine zipper motif were molecular determinants for its synaptic targeting. The overexpression of the mutant of the EVH1 domain or deletion of the extreme C-terminal leucine zipper motif markedly suppressed the synaptic localization of endogenous shank but not PSD-95 or GKAP. In contrast, an overexpressed GKAP mutant lacking shank binding activity had no effect on the synaptic localization of shank. Actin depolymerization by latrunculin A reduced the synaptic localization of PSD-Zip45, shank, and F-actin but not of PSD-95 or GKAP. Overexpression of PSD-Zip45 enhanced the accumulation of synaptic F-actin. Additionally, overexpression of PSD-Zip45 and an isoform of shank induced synaptic enlargement in association with the further accumulation of synaptic F-actin. The EVH1 domain and extreme C-terminal leucine zipper motif of PSD-Zip45 were also critical for these events. Thus, these data suggest that the PSD-Zip45-shank and PSD-95-GKAP complexes form different synaptic compartments, and PSD-Zip45 alone or PSD-Zip45-shank is involved in the synaptic accumulation of F-actin.
Usui
Shinichi
S
Department of Neuroscience (D13), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Japan.
Konno
Daijiro
D
Hori
Kei
K
Maruoka
Hisato
H
Okabe
Shigeo
S
Fujikado
Takashi
T
Tano
Yasuo
Y
Sobue
Kenji
K
D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D054637:Dual-Specificity Phosphatases; D000072233:Homer Scaffolding Proteins; D007150:Immunohistochemistry; D009419:Nerve Tissue Proteins; D009479:Neuropeptides / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D051381:Rats; D013569:Synapses / Q000737:chemistry / Q000378:metabolism*
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C120531:Shank1 protein, rat; D010749:Phosphoprotein Phosphatases; C489855:dual specificity phosphatase 12; D054637:Dual-Specificity Phosphatases