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Dec 5, 2007

Researchers Identify Protein’s Role in Synapse Formation

  • Cdk5, which helps new neurons form and migrate to their correct positions during brain development, is essential for recruiting CASK, a key scaffolding protein, for early-stage synapse development, according to MIT’s Picower Institute for Learning and Memory.

    Previous research found mutations in the genes responsible for Cdk5 and CASK in mental retardation patients and that Cdk5 plays a role in the synapse development. The MIT team thus decided to look into how Cdk5 interacts with synapse-inducing proteins, in particular CASK. 

    “We found that Cdk5 is critical for recruiting CASK to do its job for developing synapses,” reports Li-Huei Tsai, Ph.D., Picower professor of neuroscience.  “Without Cdk5, CASK was not in the right place at the right time and failed to interact with essential presynaptic components. This, in turn, led to problems with calcium influx.” The flow of calcium in and out of neurons affects processes central to nervous system development and plasticity.

    The scientists also found that the problem with CASK recruitment created the same results as those seen in gene mutations/deletions in synaptic cell surface proteins as well as neurexins and neuroligins that have been associated with autism.

    The research is published in the December 6 issue of Neuron.



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