Signaling by Chondroitin Sulfate Proteoglycans

硫酸软骨素蛋白多糖发出的信号

• 批准号: 10699709
• 负责人: HERBERT M. GELLER
• 金额: $ 83.4万
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10699709
• 关键词: Adhesions; Affect; Animal Model; Astrocytes; Central Nervous System; Chondroitin Sulfate Proteoglycan; Cicatrix; Core Protein; Cytoskeleton; Goals; Guanosine Triphosphate Phosphohydrolases; Injury; Investigation; Membrane; Modification; Natural regeneration; Nerve Regeneration; Neuronal Plasticity; Neurons; Paper; Peptide Hydrolases; Phosphoric Monoester Hydrolases; Process; Property; Proteins; Publishing; Receptor Activation; Role; Signal Transduction; Site; chondroitin sulfate glycosaminoglycan; experimental study; extracellular; inorganic phosphate; lipid phosphate phosphatase; receptor; rhoB p20 GDI; sugar

We demonstrated the the Lipid Phosphate Phosphatase-Related Proteins (PLPPRs) can modulate neuronal adhesion and the cytoskeleton through interactions with RhoGDI that modulated both RhoA and Rac1 GTPases. Papers describing these results have been published. PLPPRs, like many transmembrane receptors, are cleaved at an extracellular site near the membrane. We have now demonstrated that this cleavage is through a furin-like protease. The cleavage releases a fragment of the original receptor that associates with other transmembrane molecules. In addition, we showed that this cleavage can be regulated. Further experiments will determine the exact role of cleavage in modulating signal transduction.

我们证明了脂质磷酸磷酸酶相关蛋白（PLPPRs）可以通过与RhoGDI的相互作用来调节神经元的粘附和细胞骨架，RhoGDI可以调节RhoA和Rac1 GTP酶。 描述这些结果的论文已经发表。 PLPPR，像许多跨膜受体一样，在膜附近的细胞外位点被切割。 我们现在已经证明，这种切割是通过弗林蛋白酶样蛋白酶。 切割释放出与其他跨膜分子结合的原始受体片段。 此外，我们发现这种切割是可以调节的。 进一步的实验将确定切割在调节信号转导中的确切作用。

项目成果

The lipid phosphatase-like protein PLPPR1 associates with RhoGDI1 to modulate RhoA activation in response to axon growth inhibitory molecules.

• DOI: 10.1111/jnc.15271
• 发表时间: 2021-05
• 期刊: Journal of neurochemistry
• 影响因子: 4.7
• 作者: Agbaegbu Iweka C;Hussein RK;Yu P;Katagiri Y;Geller HM
• 通讯作者: Geller HM

Parkin targets NOD2 to regulate astrocyte endoplasmic reticulum stress and inflammation.

• DOI: 10.1002/glia.23482
• 发表时间: 2018-11
• 期刊: Glia
• 影响因子: 6.2
• 作者: Singh K;Han K;Tilve S;Wu K;Geller HM;Sack MN
• 通讯作者: Sack MN

Global analysis of neuronal phosphoproteome regulation by chondroitin sulfate proteoglycans.

• DOI: 10.1371/journal.pone.0059285
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Yu P;Pisitkun T;Wang G;Wang R;Katagiri Y;Gucek M;Knepper MA;Geller HM
• 通讯作者: Geller HM

Effect of chondroitin sulfate proteoglycans on neuronal cell adhesion, spreading and neurite growth in culture.

硫酸软骨素蛋白聚糖对培养物中神经元细胞粘附、扩散和神经突生长的影响。

• DOI: 10.4103/1673-5374.226398
• 发表时间: 2018-03
• 期刊: Neural regeneration research
• 影响因子: 6.1
• 作者: Jin J;Tilve S;Huang Z;Zhou L;Geller HM;Yu P
• 通讯作者: Yu P

Myosin II activity regulates neurite outgrowth and guidance in response to chondroitin sulfate proteoglycans.

• DOI: 10.1111/j.1471-4159.2011.07638.x
• 发表时间: 2012-03
• 期刊: Journal of neurochemistry
• 影响因子: 4.7
• 作者: Yu P;Santiago LY;Katagiri Y;Geller HM
• 通讯作者: Geller HM