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Protein kinase D promotes plasticity-induced F-actin stabilization in dendritic spines and regulates memory formation.

Bencsik N, Szíber Z, Liliom H, Tárnok K, Borbély S, Gulyás M, Rátkai A, Szűcs A, Hazai-Novák D, Ellwanger K, Rácz B, Pfizenmaier K, Hausser A, Schlett K - J. Cell Biol. (2015)

Bottom Line: In nonneuronal cells, protein kinase D (PKD) has an important role in stabilizing F-actin via multiple molecular pathways.Consequently, impaired PKD functions attenuate activity-dependent changes in hippocampal dendritic spines, including LTP formation, cause morphological alterations in vivo, and have deleterious consequences on spatial memory formation.We thus provide compelling evidence that PKD controls synaptic plasticity and learning by regulating actin stability in dendritic spines.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology and Neurobiology, Eötvös Loránd University, H-1117 Budapest, Hungary.

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Expression of the dominant-negative kdPKD-EGFP mutant in double transgenic hippocampal neurons alters dendritic spine morphology in vivo. (A–I) a-EGFP staining in hippocampal CA1 (A–E) and CA3 (F–I) pyramidal neurons from kdPKD-EGFP–expressing (A, C–F, and H) or control mice (B, G, and I). (A, B, F, and G) Light microscopic DAB immunohistochemistry. (C, H, and I) Black arrows point to a-EGFP DAB precipitates in the dendritic spines of CA1 and CA3 dendrites, respectively. Nonlabeled spines are also present in the sections of kdPKD-EGFP mutant mice (white arrows in C and I). (D and E) Electron micrographs showing pre-embedded immunogold anti-GFP labeling (arrowheads) in the CA1 region. Bars: (A, B, F, and G) 30 µm; (C–E, H, and I) 200 nm. (J–M) Quantitative evaluation of the dendritic spines in the CA1 (J and L; 144 control and 114 kdPKD-EGFP spines) and CA3 (K and M; 142 control and 153 kdPKD-EGFP spines) regions of control and kdPKD-EGFP–expressing hippocampus. Pearson correlation values between spine profile area and PSD length are indicated in J and K. Graphs represent mean ± SEM. *, P < 0.05; ***, P < 0.001.
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fig4: Expression of the dominant-negative kdPKD-EGFP mutant in double transgenic hippocampal neurons alters dendritic spine morphology in vivo. (A–I) a-EGFP staining in hippocampal CA1 (A–E) and CA3 (F–I) pyramidal neurons from kdPKD-EGFP–expressing (A, C–F, and H) or control mice (B, G, and I). (A, B, F, and G) Light microscopic DAB immunohistochemistry. (C, H, and I) Black arrows point to a-EGFP DAB precipitates in the dendritic spines of CA1 and CA3 dendrites, respectively. Nonlabeled spines are also present in the sections of kdPKD-EGFP mutant mice (white arrows in C and I). (D and E) Electron micrographs showing pre-embedded immunogold anti-GFP labeling (arrowheads) in the CA1 region. Bars: (A, B, F, and G) 30 µm; (C–E, H, and I) 200 nm. (J–M) Quantitative evaluation of the dendritic spines in the CA1 (J and L; 144 control and 114 kdPKD-EGFP spines) and CA3 (K and M; 142 control and 153 kdPKD-EGFP spines) regions of control and kdPKD-EGFP–expressing hippocampus. Pearson correlation values between spine profile area and PSD length are indicated in J and K. Graphs represent mean ± SEM. *, P < 0.05; ***, P < 0.001.

Mentions: To assess neuron-specific functions of PKD in vivo, we used a transgenic TetOn mouse line, allowing inducible expression of the dominant-negative kdPKD-EGFP protein (Czöndör et al., 2009). For better readability, doxycycline (DOX)-treated CaMKIIα-rtTA2 × kdPKD-EGFP double transgenic mice are named kdPKD-EGFP–expressing mice, whereas single transgenic littermates treated with DOX are referred to as the control group (Fig. 4, and Fig. 5, and Fig. S3).


Protein kinase D promotes plasticity-induced F-actin stabilization in dendritic spines and regulates memory formation.

Bencsik N, Szíber Z, Liliom H, Tárnok K, Borbély S, Gulyás M, Rátkai A, Szűcs A, Hazai-Novák D, Ellwanger K, Rácz B, Pfizenmaier K, Hausser A, Schlett K - J. Cell Biol. (2015)

Expression of the dominant-negative kdPKD-EGFP mutant in double transgenic hippocampal neurons alters dendritic spine morphology in vivo. (A–I) a-EGFP staining in hippocampal CA1 (A–E) and CA3 (F–I) pyramidal neurons from kdPKD-EGFP–expressing (A, C–F, and H) or control mice (B, G, and I). (A, B, F, and G) Light microscopic DAB immunohistochemistry. (C, H, and I) Black arrows point to a-EGFP DAB precipitates in the dendritic spines of CA1 and CA3 dendrites, respectively. Nonlabeled spines are also present in the sections of kdPKD-EGFP mutant mice (white arrows in C and I). (D and E) Electron micrographs showing pre-embedded immunogold anti-GFP labeling (arrowheads) in the CA1 region. Bars: (A, B, F, and G) 30 µm; (C–E, H, and I) 200 nm. (J–M) Quantitative evaluation of the dendritic spines in the CA1 (J and L; 144 control and 114 kdPKD-EGFP spines) and CA3 (K and M; 142 control and 153 kdPKD-EGFP spines) regions of control and kdPKD-EGFP–expressing hippocampus. Pearson correlation values between spine profile area and PSD length are indicated in J and K. Graphs represent mean ± SEM. *, P < 0.05; ***, P < 0.001.
© Copyright Policy - openaccess
Related In: Results  -  Collection

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fig4: Expression of the dominant-negative kdPKD-EGFP mutant in double transgenic hippocampal neurons alters dendritic spine morphology in vivo. (A–I) a-EGFP staining in hippocampal CA1 (A–E) and CA3 (F–I) pyramidal neurons from kdPKD-EGFP–expressing (A, C–F, and H) or control mice (B, G, and I). (A, B, F, and G) Light microscopic DAB immunohistochemistry. (C, H, and I) Black arrows point to a-EGFP DAB precipitates in the dendritic spines of CA1 and CA3 dendrites, respectively. Nonlabeled spines are also present in the sections of kdPKD-EGFP mutant mice (white arrows in C and I). (D and E) Electron micrographs showing pre-embedded immunogold anti-GFP labeling (arrowheads) in the CA1 region. Bars: (A, B, F, and G) 30 µm; (C–E, H, and I) 200 nm. (J–M) Quantitative evaluation of the dendritic spines in the CA1 (J and L; 144 control and 114 kdPKD-EGFP spines) and CA3 (K and M; 142 control and 153 kdPKD-EGFP spines) regions of control and kdPKD-EGFP–expressing hippocampus. Pearson correlation values between spine profile area and PSD length are indicated in J and K. Graphs represent mean ± SEM. *, P < 0.05; ***, P < 0.001.
Mentions: To assess neuron-specific functions of PKD in vivo, we used a transgenic TetOn mouse line, allowing inducible expression of the dominant-negative kdPKD-EGFP protein (Czöndör et al., 2009). For better readability, doxycycline (DOX)-treated CaMKIIα-rtTA2 × kdPKD-EGFP double transgenic mice are named kdPKD-EGFP–expressing mice, whereas single transgenic littermates treated with DOX are referred to as the control group (Fig. 4, and Fig. 5, and Fig. S3).

Bottom Line: In nonneuronal cells, protein kinase D (PKD) has an important role in stabilizing F-actin via multiple molecular pathways.Consequently, impaired PKD functions attenuate activity-dependent changes in hippocampal dendritic spines, including LTP formation, cause morphological alterations in vivo, and have deleterious consequences on spatial memory formation.We thus provide compelling evidence that PKD controls synaptic plasticity and learning by regulating actin stability in dendritic spines.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology and Neurobiology, Eötvös Loránd University, H-1117 Budapest, Hungary.

Show MeSH
Related in: MedlinePlus