Despite these observations, until now there has been no evidence that specific deletions of d-catenin were sufficient to produce cognitive deficits. Also, although adhesion proteins have been shown to be critical for synaptic plasticity, a process by which brain circuits can be modified during learning, it has been unknown wether deletions of d-catenin would alter this process.
In the new work, researchers Inbal Israely and Xin Liu at UCLA show that mice with deletions of d-catenin display severe learning and memory deficits and thereby establish a causal link between deletions of d-catenin and cognitive dysfunction. This finding is particularly interesting because other adhesion proteins can be found in the brain, but only d-catenin is found specifically in neurons. The researchers also show that deletion of d-catenin produces severe deficits in short-lasting and long-lasting synaptic plasticity. In addition, they show that the synaptic composition of mutant animals is altered: the expression of several proteins involved in synaptic connectivity and plasticity is reduced in neurons from d-catenin mutant animals, possibly offering a clue to the mechanisms by which deletions of d-catenin cause synaptic and cognitive dysfunction. Ultimately, this work may facilitate the understanding of the mental retardation observed in Cri-du-Chat Syndrome and the memory deficits observed in Familial Alzheimer's disease.
Inbal Israely, Rui M. Costa, Cui Wei Xie, Alcino J. Silva, Kenneth S. Kosik, and Xin Liu: "Deletion of the Neuron-Specific Protein delta-catenin Leads to Severe Cognitive and Synaptic Dysfunction"
Publishing in Current Biology , Volume 14, Number 18, September 21, 2004, pages 1657–1663.
Current Biology