δ-Catenin Regulates Spine Architecture via Cadherin and PDZ-dependent Interactions.
The ability of neurons to maintain spine architecture and modulate it in response to synaptic activity is a crucial component of the cellular machinery that underlies information storage in pyramidal neurons of the hippocampus. Here we show a critical role for δ-catenin, a component of the cadherin-catenin cell adhesion complex, in regulating spine head width and length in pyramidal neurons of the hippocampus. The loss of Ctnnd2, the gene encoding δ-catenin, has been associated with the intellectual disability observed in the cri du chat syndrome, suggesting that the functional roles of δ-catenin are vital for neuronal integrity and higher order functions. We demonstrate that loss of δ-catenin in a mouse model or knockdown of δ-catenin in pyramidal neurons compromises spine head width and length, without altering spine dynamics. This is accompanied by a reduction in the levels of synaptic N-cadherin. The ability of δ-catenin to modulate spine architecture is critically dependent on its ability to interact with cadherin and PDZ domain-containing proteins. We propose that loss of δ-catenin during development perturbs synaptic architecture leading to developmental aberrations in neural circuit formation that contribute to the learning disabilities in a mouse model and humans with cri du chat syndrome.
From the Department of Pharmacology and Experimental Neuroscience.
Li
L
Yuan
Developmental Neuroscience, Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198.
Eunju
E
Seong
Developmental Neuroscience, Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198.
James L
JL
Beuscher
From the Department of Pharmacology and Experimental Neuroscience, Developmental Neuroscience, Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198 Jyothi.arikkath@unmc.edu.
Jyothi
J
Arikkath
D000818:Animals; D051186:Armadillo Domain Proteins / Q000235:genetics / Q000378:metabolism*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D051177:Catenins / Q000235:genetics / Q000378:metabolism*; D003410:Cri-du-Chat Syndrome / Q000196:embryology / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D017966:Pyramidal Cells / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D013131:Spine / Q000196:embryology* / Q000473:pathology; D013569:Synapses / Q000378:metabolism*; D000095002:Delta Catenin
D051186:Armadillo Domain Proteins; D015820:Cadherins; D051177:Catenins; C489083:Cdh2 protein, mouse; C484654:Ctnnd2 protein, rat; C570099:N-cadherin, rat; D009419:Nerve Tissue Proteins; D000095002:Delta Catenin
Cadherin; Catenin; Dendritic Spine; Hippocampus; Neuron; PDZ; Spine Architecture; Spine Dynamic