February 13, 2009

Understanding the Chemical Basis of Neuronal Development and Communication

Cristal Gama

Understanding the Chemical Basis of Neuronal Development and Communication Although carbohydrates are known to participate in many processes including inflammation and cancer metastasis, their functional roles are only beginning to be understood on a molecular level. The challenge is that carbohydrates and glycoproteins are inherently difficult to study. Unlike DNA and proteins, carbohydrate structures are not template-encoded, and are challenging to detect in vivo and manipulate for structure-function analyses. New tools are needed to complement biochemical and genetic approaches in order to advance our understanding of carbohydrates and their physiological roles. Here, we will focus on how two types of carbohydrates, fucosyl saccharides and chondroitin sulfate glycosaminoglycans, mediate molecular recognition events essential for neuronal communication and development. Specifically, we established that fucose-associated proteins participate in a novel carbohydrate-mediated pathway for regulating neuronal growth. Additionally, we developed a chemical approach to evaluate the structure-activity relationship of chondroitin sulfate and have demonstrated that the chondroitin sulfate-E sulfation sequence is a stimulatory motif that promotes the growth of several neuron types. Cristal I. Gama and Linda C. Hsieh-Wilson. “Chemical approaches to deciphering the glycosaminoglycan code.” Curr. Opin. Chem. Biol., 2005, 9, 609. Stacey A. Kalovidouris, Cristal I. Gama, Lori W. Lee, and Linda C. Hsieh-Wilson. “A role for fucose ?(1-2) galactose carboydrates in neuronal growth.” J. Am. Chem. Soc., 2005, 127, 1340. Cristal I. Gama, Sarah E. Tully, Naoki Sotogaku, Peter M. Clark, Manish Rawat, Nagarajan Vaidehi, William A. Goddard, III, Akinori Nishi, and Linda C. Hsieh-Wilson. “Sulfation patterns of glycosaminoglycans encode molecular recognition and activity.” Nat. Chem. Biol., 2006, 2, 467.