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Structure/Function Relationships of Glycosaminoglycan Chains

GAG Chain Receptors

Intracellular Signaling Pathways

Astrocyte Extracellular Matrix

Biophysics of Growth Cones

Tissue Engineering

Lab Protocols

Laboratory of Developmental Neurobiology
Division of Intramural Research, NHLBI
Bethesda, MD 20892-1754

Geller Lab Research > Proteoglycan Glycosaminoglycan Chains

Structhre of Glycosaminoglycan Chains

Proteoglycans are comprised of a core protein decorated by one or more glycosaminoglycan (GAG) chains.  GAG chains are attached to the serine of a core protein through a linkage region of Xyl-Gly-Gly.  The remainder of the GAG chain is comprised of an alternating series of GlcA-GalNAc sugars.  Some of the GlcA residues are epimerized to IdoA, while either of the two sugars in a disaccharide pair can be sulfate on any of several positions.  The length of the GAG chain and the position of sulfation are not template-driven, leading to an enormous number of possible permutations.  Our research has demonstrated that the GAG chains are essential for signaling guidance cues to neurons: elimination of GAG chains or preventing their synthesis reduces the biological activity of chondroitin sulfate proteoglycans.  Moreover, our recent research has shown that CSPG signaling is dependent on 4-sulfation of GalNAc, especially at the non-reducing end (the furthest from the protein core).  Reducing terminal 4-sulfation with the enzyme arylsulfatase B can significantly alter the actions of CSPGs.  Future research is directed at appyling this discovery to promote recovery of function after spinal cord or brain injury.   

• Pearson, C. S., Mencio, C. P., Barber, A. C., Martin, K. R. and Geller, H. M. Identification of a critical sulfation in chondroitin that inhibits axonal regeneration, eLife, 7:e37139, 2018. [link]

• Yu, P., Pearson, C. S., Geller, H. M. Flexible roles for proteoglycan sulfation and receptor signaling, Trends Neurosci.,  41:47-61, 2018. [abstract]

• Janecke, A. R., Li, B., Boehm, M., Krabichler, B., Rohrbach, M., Müller, T., Fuchs, I., Golas, G., Katagiri, Y. Ziegler, S. G., Gahl, W. A., Wilnai, Y., Zoppi, N., Geller, H. M., Giunta, C., Slavotinek, A., Steinmann, B. The phenotype of the musculocontractural type of Ehlers-Danlos syndrome due to CHST14 mutations, Am. J. Med. Genetics Part A, 2015. [abstract]

• Susarla, B. T. S., Laing, E. D., Yu, P., Katagiri, Y., Geller, H. M. and Symes, A. J. SMAD proteins differentially regulate TGF-β mediated induction of chondroitin sulfate proteoglycans, J. Neurochem., 119:868-78, 2011.  [abstract]

• Wang, H., Katagiri, Y., McCann, T. E., Unsworth, E., Goldsmith, P., Yu, Z.-Y., Tan, F., Mills, E. M., Wang, Y., Symes, A. J. and Geller, H. M. 4-sulfation of chondroitin is critical for inhibition of axonal growth, J. Cell Sci., 121:3083-3091, 2008. [abstract]

• Laabs, T., Wang, H., McCann, T. E., Katagiri, Y., Fawcett, J. W . and Geller, H. M. Inhibiting GAG chain polymerization decreases the inhibitory activity of astrocyte-derived chondroitin sulfate proteoglycans, J. Neurosci., 27:14494-14501, 2007.  [abstract]

• Powell, E. M., Fawcett, J. W. and Geller, H. M. Neurite guidance by astrocyte proteoglycans, Mol. Cell. Neurosci., 10:27-42, 1997. [abstract]