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Structure/Function Relationships of Glycosaminoglycan Chains

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 > Intracellular Signaling Pathways

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.  The major cytoskeletal proteins in growth cones are actin, myosin and tubulin.  Our research has demonstrated alterations in the rate of tubulin polymerization as neurites encounter CSPGs.  We later found that inhibition of myosin II function with blebbistatin can increase axonal growth on CSPG substrates.  While these targeted approaches determined the involvement of these known proteins, a more global approach to identify proteins whose phosphorylation was changed in response to CSPG application resulted in the identificaiton of many different classes of proteins, not only cytoskeletal, involved in the response to CSPGs.  The protein whose phosphorylation was most altered was Lipid Protein Phosphatase Related protein-1, also known as Plasticity Related Gene-3.  Further proteomic experiments determined that LPPR1 interacts with other members of the LPPR family to mediate their biological actions.  Our current research is to investigate the biology and mechanism of action of the LPPR proteins using cell biological and transgenic approaches.

• Yu, P., Agbaegbu, C., Malide, D., Wu, X., Katagiri, Y., Hammer, J. A. and Geller, H. M. Cooperative interactions of LPPR/PRG family members in membrane localization and alteration of cellular morphology, J. Cell Sci., pii: jcs.169789, 2015.

• Yu, P., Pisitkun, T., Wang, G., Wang, R., Katagiri, Y., Gucek, M., Knepper, M. A. and Geller, H. M. Global analysis of neuronal phosphoproteome regulation by chondroitin sulfate proteoglycans, PLoS One, 8:e59285, 2013.

• Yu, P., Santiago, L. Y., Wang, H., Katagiri, Y. and Geller, H. M. Myosin II activity regulates neurite outgrowth and guidance in response to chondroitin sulfate proteoglycans., J. Neurochem., 120:1117-1128, 2012.

• Kelly, T.-A. N., Katagiri, Y., Kumar, P., Chen, I.-I., Vartanian, K. B., Rosoff, W. J., Urbach, J. S. and Geller, H. M. Localized alteration of microtubule polymerization in growth cones at inhibitory boundaries, J. Neurosci. Res., 88:3024-33, 2010.