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Cadherin activity is required for activity-induced spine remodeling.

Okamura K, Tanaka H, Yagita Y, Saeki Y, Taguchi A, Hiraoka Y, Zeng LH, Colman DR, Miki N - J. Cell Biol. (2004)

Bottom Line: N-cadherin-venus fusion protein laterally dispersed along the expanding spine head.Overexpression of dominant-negative forms of N-cadherin resulted in the abrogation of the spine expansion.Inhibition of actin polymerization with cytochalasin D abolished the spine expansion.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Osaka University Medical School, Suita, Japan.

ABSTRACT
Neural activity induces the remodeling of pre- and postsynaptic membranes, which maintain their apposition through cell adhesion molecules. Among them, N-cadherin is redistributed, undergoes activity-dependent conformational changes, and is required for synaptic plasticity. Here, we show that depolarization induces the enlargement of the width of spine head, and that cadherin activity is essential for this synaptic rearrangement. Dendritic spines visualized with green fluorescent protein in hippocampal neurons showed an expansion by the activation of AMPA receptor, so that the synaptic apposition zone may be expanded. N-cadherin-venus fusion protein laterally dispersed along the expanding spine head. Overexpression of dominant-negative forms of N-cadherin resulted in the abrogation of the spine expansion. Inhibition of actin polymerization with cytochalasin D abolished the spine expansion. Together, our data suggest that cadherin-based adhesion machinery coupled with the actin-cytoskeleton is critical for the remodeling of synaptic apposition zone.

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AMPA receptor activation is involved in the spine expansion. (A) Time-lapse imaging of GFP-filled spines was performed in the presence of glutamate receptor antagonist, CNQX or APV. CNQX but not APV blocked the depolarization-induced spine expansion. (B) The SCCL of each spine before and 30 min after depolarization is plotted. *P < 0.003. (C) The ratios between resting SCCL and stimulated (30 min) SCCL are shown (mean ± SEM). **P < 0.05 to control and +APV. The measurements of 42 (control), 19 (CNQX), and 34 (APV) spines of four neurons (dendrites) were collected from four independent experiments. Bar, 2.50 μm.
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fig4: AMPA receptor activation is involved in the spine expansion. (A) Time-lapse imaging of GFP-filled spines was performed in the presence of glutamate receptor antagonist, CNQX or APV. CNQX but not APV blocked the depolarization-induced spine expansion. (B) The SCCL of each spine before and 30 min after depolarization is plotted. *P < 0.003. (C) The ratios between resting SCCL and stimulated (30 min) SCCL are shown (mean ± SEM). **P < 0.05 to control and +APV. The measurements of 42 (control), 19 (CNQX), and 34 (APV) spines of four neurons (dendrites) were collected from four independent experiments. Bar, 2.50 μm.

Mentions: Dendritic spines comprise an excitatory postsynaptic structure equipped with glutamate receptors. To see if the lateral spine enlargement is coupled with excitatory synaptic functions, we tried to identify the pathway responsible for the phenomenon. In the presence of an AMPA receptor antagonist CNQX (100 μM), neither spine shrinkage during depolarization, nor spine enlargement after recovery occurred (Fig. 4). The mean SCCL being 3.41 ± 0.175 μm at rest remained 3.38 ± 0.160 μm in 30 min of recovery. In contrast, an NMDA receptor antagonist APV (100 μM) did not strongly affect these responses of the spines (Fig. 4). The mean SCCL changed from 2.63 ± 0.103 μm to 3.08 ± 0.112 μm in 30 min of recovery. The data suggest that the broadening of spine head is under the influence of AMPA-type glutamate receptor activation. The observation is consistent with the hypothesis that the rapid rearrangement of the synaptic adhesion zone might be related to the rapid phase of synaptic plasticity.


Cadherin activity is required for activity-induced spine remodeling.

Okamura K, Tanaka H, Yagita Y, Saeki Y, Taguchi A, Hiraoka Y, Zeng LH, Colman DR, Miki N - J. Cell Biol. (2004)

AMPA receptor activation is involved in the spine expansion. (A) Time-lapse imaging of GFP-filled spines was performed in the presence of glutamate receptor antagonist, CNQX or APV. CNQX but not APV blocked the depolarization-induced spine expansion. (B) The SCCL of each spine before and 30 min after depolarization is plotted. *P < 0.003. (C) The ratios between resting SCCL and stimulated (30 min) SCCL are shown (mean ± SEM). **P < 0.05 to control and +APV. The measurements of 42 (control), 19 (CNQX), and 34 (APV) spines of four neurons (dendrites) were collected from four independent experiments. Bar, 2.50 μm.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2172468&req=5

fig4: AMPA receptor activation is involved in the spine expansion. (A) Time-lapse imaging of GFP-filled spines was performed in the presence of glutamate receptor antagonist, CNQX or APV. CNQX but not APV blocked the depolarization-induced spine expansion. (B) The SCCL of each spine before and 30 min after depolarization is plotted. *P < 0.003. (C) The ratios between resting SCCL and stimulated (30 min) SCCL are shown (mean ± SEM). **P < 0.05 to control and +APV. The measurements of 42 (control), 19 (CNQX), and 34 (APV) spines of four neurons (dendrites) were collected from four independent experiments. Bar, 2.50 μm.
Mentions: Dendritic spines comprise an excitatory postsynaptic structure equipped with glutamate receptors. To see if the lateral spine enlargement is coupled with excitatory synaptic functions, we tried to identify the pathway responsible for the phenomenon. In the presence of an AMPA receptor antagonist CNQX (100 μM), neither spine shrinkage during depolarization, nor spine enlargement after recovery occurred (Fig. 4). The mean SCCL being 3.41 ± 0.175 μm at rest remained 3.38 ± 0.160 μm in 30 min of recovery. In contrast, an NMDA receptor antagonist APV (100 μM) did not strongly affect these responses of the spines (Fig. 4). The mean SCCL changed from 2.63 ± 0.103 μm to 3.08 ± 0.112 μm in 30 min of recovery. The data suggest that the broadening of spine head is under the influence of AMPA-type glutamate receptor activation. The observation is consistent with the hypothesis that the rapid rearrangement of the synaptic adhesion zone might be related to the rapid phase of synaptic plasticity.

Bottom Line: N-cadherin-venus fusion protein laterally dispersed along the expanding spine head.Overexpression of dominant-negative forms of N-cadherin resulted in the abrogation of the spine expansion.Inhibition of actin polymerization with cytochalasin D abolished the spine expansion.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Osaka University Medical School, Suita, Japan.

ABSTRACT
Neural activity induces the remodeling of pre- and postsynaptic membranes, which maintain their apposition through cell adhesion molecules. Among them, N-cadherin is redistributed, undergoes activity-dependent conformational changes, and is required for synaptic plasticity. Here, we show that depolarization induces the enlargement of the width of spine head, and that cadherin activity is essential for this synaptic rearrangement. Dendritic spines visualized with green fluorescent protein in hippocampal neurons showed an expansion by the activation of AMPA receptor, so that the synaptic apposition zone may be expanded. N-cadherin-venus fusion protein laterally dispersed along the expanding spine head. Overexpression of dominant-negative forms of N-cadherin resulted in the abrogation of the spine expansion. Inhibition of actin polymerization with cytochalasin D abolished the spine expansion. Together, our data suggest that cadherin-based adhesion machinery coupled with the actin-cytoskeleton is critical for the remodeling of synaptic apposition zone.

Show MeSH
Related in: MedlinePlus