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Intracellular Scaffold Proteins

Broadly defined, these are proteins that reside inside a cell and whose primary function is to help assemble complexes with other proteins that facilitate signal pathway activation. By assembling specific proteins that work together in a certain way, scaffold proteins can direct responses to signals from neighboring cells - that is, by favoring activation of one downstream biochemical pathway versus another. We have focused on a set of closely partnering intracellular scaffold proteins:
Dapper Antagonist of Catenin (Dact), Dishevelled (Dvl) and SEC14 and Spectrin Domains-1 (Sestd1).

The diagram below depicts cube-shaped cells in a simplified epithelium that contain these proteins and biochemical signaling pathways.

Wnt scaffold proteins in cells

Interactions between the intracellular Dvl , Dact, and Sestd1 proteins, including the formation of regulatory complexes with transmembrane, cytoskeletal, and other cytoplasmic proteins, help determine the cellular response to a signal (a Wnt glycoprotein) coming from outside (from neighboring cells).

These proteins and biochemical pathways are present in many epithelial tissues of the embryo. Developing neurons start out in a simple epithelium but migrate and mature into far more complex forms in the brain. Even so, neurons use these same biochemical pathways to control their shape, orientation, adhesion, and to communicate with their neighbors into adulthood.

By uncovering how these proteins and biochemical pathways work, we aim to better understand their contributions to both normal and abnormal development in the human embryo and the brain. Our research has implications for understanding the origins of complex birth defects, other diseases including cancer, and can help clarify how major psychiatric conditions such as autism, schizophrenia, major depression and bipolar disorder emerge and progress.

This will lead to more effective methods to diagnose and treat all of these conditions.

The favorite experimental tools of the Cheyette laboratory are recombinant DNA technology, tissue culture, and
genetic engineering in mice coupled with developmental and behavioral analyses of these animals.

Here is a recent journal cover highlighting this type of research from our lab: Yang & Cheyette 2013


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