We have conducted studies showing that the the LAR family of receptor protein tyrosine phosphatases are are binding partners for proteoglycan GAG chains. The binding of the different family members are not all the same. We have identified different regions in the extracellular domains of these molecules that bind GAG chains with different sulfation patterns. We have identified a novel binding site in Receptor Protein Tyrosine Phosphatase Sigma that binds Heparin Sulfate. In addition our data point to an additional receptor that binds bioactive CSPGs. A publication describing these results is in preparation. We demonstrated the the Lipid Phosphate Phosphatase-Related Proteins (LPPRs) act in concert to modulate cellular physiology. We find that they associate with each other in cells, and that this association increases the bioactivity of these proteins. A paper describing these results was published. We have created knockout mice for the LPPR-1 and LPPR-3 and are now characterizing these mice. We have found that xylosides, compounds that are used to alter proteoglycan GAG chain composition, have significant actions at concentrations lower than those previously reported to reduce GAG chains can alter growth cone morphology. Evidence points to a novel signaling mechanism triggered by xylsides only at low concentrations. In collaboration with Dr. Jeffrey Urbach of Georgetown University, we are investigating the role of stiffness in controlling axonal growth. We have shown than neurons grow differently on substrates of different stiffness, and are now investigating the role of stiffness in neuronal guidance.

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Project End
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Budget End
Support Year
8
Fiscal Year
2016
Total Cost
Indirect Cost
Name
U.S. National Heart Lung and Blood Inst
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Jin, Jingyu; Tilve, Sharada; Huang, Zhonghai et al. (2018) Effect of chondroitin sulfate proteoglycans on neuronal cell adhesion, spreading and neurite growth in culture. Neural Regen Res 13:289-297
Katagiri, Yasuhiro; Morgan, Ashlea A; Yu, Panpan et al. (2018) Identification of novel binding sites for heparin in receptor protein-tyrosine phosphatase (RPTP?): Implications for proteoglycan signaling. J Biol Chem 293:11639-11647
Yu, Panpan; Pearson, Craig S; Geller, Herbert M (2018) Flexible Roles for Proteoglycan Sulfation and Receptor Signaling. Trends Neurosci 41:47-61
Yi, Mengni; Wei, Tianjiao; Wang, Yanxia et al. (2017) The potassium channel KCa3.1 constitutes a pharmacological target for astrogliosis associated with ischemia stroke. J Neuroinflammation 14:203
Shumakovich, Marina A; Mencio, Caitlin P; Siglin, Jonathan S et al. (2017) Astrocytes from the brain microenvironment alter migration and morphology of metastatic breast cancer cells. FASEB J :
Yi, Mengni; Yu, Panpan; Lu, Qin et al. (2016) KCa3.1 constitutes a pharmacological target for astrogliosis associated with Alzheimer's disease. Mol Cell Neurosci 76:21-32
Janecke, Andreas R; Li, Ben; Boehm, Manfred et al. (2016) The phenotype of the musculocontractural type of Ehlers-Danlos syndrome due to CHST14 mutations. Am J Med Genet A 170A:103-15
Polackwich, Robert J; Koch, Daniel; McAllister, Ryan et al. (2015) Traction force and tension fluctuations in growing axons. Front Cell Neurosci 9:417
Yu, Panpan; Agbaegbu, Chinyere; Malide, Daniela A et al. (2015) Cooperative interactions of LPPR family members in membrane localization and alteration of cellular morphology. J Cell Sci 128:3210-22
Yu, Zhihua; Yu, Panpan; Chen, Hongzhuan et al. (2014) Targeted inhibition of KCa3.1 attenuates TGF-?-induced reactive astrogliosis through the Smad2/3 signaling pathway. J Neurochem 130:41-49

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