Abstract
Morphological plasticity of dendritic spines and synapses is thought to be crucial for their physiological functions. Here we show that αN-catenin, a linker between cadherin adhesion receptors and the actin cytoskeleton, is essential for stabilizing dendritic spines in rodent hippocampal neurons in culture. In the absence of αN-catenin, spine heads were abnormally motile, actively protruding filopodia from their synaptic contact sites. Conversely, αN-catenin overexpression in dendrites reduced spine turnover, causing an increase in spine and synapse density. Tetrodotoxin (TTX), a neural activity blocker, suppressed the synaptic accumulation of αN-catenin, whereas bicuculline, a GABA antagonist, promoted it. Furthermore, excess αN-catenin rendered spines resistant to the TTX treatment. These results suggest that αN-catenin is a key regulator for the stability of synaptic contacts.
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Acknowledgements
We thank T. Manabe for TTX and H. Ishigami for maintaining the mice. This work was supported by the program Grants-in-Aid for Specially Promoted Research of the Ministry of Education, Science, Sports, and Culture of Japan to M.T.
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Supplementary Fig. 1.
aN-catenin overexpression does not affect dendrite arborization. αN-cat-/- neurons were transfected with EGFP, and wild-type neurons, with either EGFP only or EGFP and αN-cat-flag at the time of plating. Dendrite branch analysis was performed at 7 DIV. In z-stacked images, the branches were traced manually by using LSM510 software; and TDBTN (total dendritic branch tip number), TDBL (total dendritic branch length), and ADBL (average dendritic branch length) were analyzed manually, according to the method described28. A total of 1026 branches in WT, 961 branches in αN-cat-/-, and 990 branches in αN-catenin-overexpressing neurons, obtained from 10 different neurons for each group, were analyzed. Data were compared by Student's t test. Histograms showing mean ± s.e.m. were constructed. (a) Normalized TDBTN in wild-type (WT), αN-cat-/-, and αN-catenin-overexpressing neurons. The raw data was 102.6 for WT, 96.1 for αN-cat-/-, and 99.0 for αN-catenin overexpression. There was no significant difference between WT and αN-cat-/- (P = 0.39) or between WT and aN-catenin-overexpressing neurons (P = 0.30) by Student's t test. (b) Normalized TDBL. The raw data was 1428.2 for WT, 1337.6 for αN-cat-/-, and 1405.5 for αN-catenin-overexpressing neurons. There was no significant difference between WT and αN-cat-/- (P = 0.44) or between WT and αN-catenin-overexpressing neurons (P = 0.29). (c) Normalized ADBL. The raw data was 14.0 for WT, 14.0 for αN-cat-/-, and 14.6 for aN-catenin-overexpressing neurons. There was no significant difference between WT and αN-cat-/- (P = 0.28) or between WT and αN-catenin-overexpressing neurons (P = 0.28). (GIF 7 kb)
Supplementary Video 1.
Time-lapse movie of an EGFP-tagged actin-transfected αN-cat+/+ neuron at 15 DIV. Images were acquired at 1-min intervals over a 95-min period. (MOV 2366 kb)
Supplementary Video 2.
Time-lapse movies of an EGFP-tagged actin-transfected αN-cat-/- neuron at 15 DIV. Images were acquired at 1-min intervals over a 95-min period. (MOV 2534 kb)
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Abe, K., Chisaka, O., van Roy, F. et al. Stability of dendritic spines and synaptic contacts is controlled by αN-catenin. Nat Neurosci 7, 357–363 (2004). https://doi.org/10.1038/nn1212
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DOI: https://doi.org/10.1038/nn1212
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