δ-Catenin Regulates Spine Architecture via Cadherin and PDZ-dependent Interactions.

Abstract

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.

• Authors: Li Yuan, Eunju Seong, James L Beuscher, Jyothi Arikkath
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 290 Issue 17 Pg. 10947-57 (Apr 24 2015) ISSN: 1083-351X [Electronic] United States
• PMID: 25724647 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical References

• Armadillo Domain Proteins
• Cadherins
• Catenins
• Cdh2 protein, mouse
• Ctnnd2 protein, rat
• N-cadherin, rat
• Nerve Tissue Proteins
• Delta Catenin

Topics

• Animals
• Armadillo Domain Proteins (genetics, metabolism)
• Cadherins (genetics, metabolism)
• Catenins (genetics, metabolism)
• Cri-du-Chat Syndrome (embryology, genetics, pathology)
• Disease Models, Animal
• Humans
• Mice
• Nerve Tissue Proteins (genetics, metabolism)
• Pyramidal Cells (metabolism, pathology)
• Rats
• Spine (embryology, pathology)
• Synapses (metabolism)
• Delta Catenin