Neurobiology in the Geller Lab  
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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 Receptors

When growth cones of neurons encounter CSPGs, they stop or alter their direction of movement.  Our major hypothesis is that CSPGs interact with receptors to initiate an intracellular signaling cascade resulting in an alteration of cytoskeletal dynamics.  Both chondroitin sulfate and heparan sulfate interact with two families of receptors: the LAR family, which includes Receptor Protein Tyrosine Phosphatase RPTP) σ RPTP-δ and the Leukocyte Common Antigen Receptor (LAR), and two members of the Nogo Receptor familiy, NgR1 and NgR3.  This leads to the question of how HS promotes growth and CS inhibits growth. We have establihed that all of these interactions depend upon sulfation: HS and highly sulfated CS bind with high affinity to all five of these receptors.  Another major issue is how binding results in alterations of signaling. We have identified diifferences in the interaction of the LAR family members with proteoglycans which may explain their differential actions on neurons.  Current research is directed at understanding the structural features of these receptors that mediate their interactions with proteoglycan GAG chains.  An additional issue is that there is no binding of these receptors to GAG chains in normal brain, suggesting that there are other ligands involved in normal brain function.  We are in the process of identifying these ligands. 

• Katagiri, Y., Morgan, A. A., Yu, P., Bangayan, N. J., Junka, R., Geller, H. M., Identification of novel binding sites for heparin in RPTPσ: Implications for proteoglycan signaling, J. Biol. Chem., 293:11639-11647, 2018.

• Yi, J. H., Katagiri, Y., Yu, P., Lourie, J., Bangayan, N. J., Symes, A. J. and Geller, H. M. Receptor protein tyrosine phosphatase σ binds to neurons in the adult mouse brain, Exptl. Neurol., 255:12-18, 2014.

• Dickendesher, T. L., Baldwin, K. T., Mironova, Y. A., Koriyama, Y., Raiker, S. J., Askew, K. L., Geoffroy, C. G., Zheng, B., Liepmann, C. D., Katagiri, Y., Benowitz, L. I., Geller, H. M., Giger, R. J. NgR1 and NgR3 are inhibitory receptors for chondroitin sulfate proteoglycans, Nature Neurosci., 15:703-12, 2012.