title: Spy1 Protein Mediates Phosphorylation and Degradation of SCG10 Protein in Axonal Degeneration.
abstract: Axon loss is a destructive consequence of a wide range of neurological diseases without a clearly defined mechanism. Recent data demonstrate that SCG10 is a novel axonal maintenance factor and that rapid SCG10 loss after injury requires JNK activity; how JNK induces degradation of SCG10 is not well known. Here we showed that SCG10 was a binding partner of Spy1, a Speedy/RINGO family protein, which participated in cellular response to sciatic nerve injury. During the early stage of axonal injury, Spy1 expression was inversely correlated with SCG10. Spy1 mediated SCG10 phosphorylation and degradation partly in a JNK-dependent manner. Inhibition of Spy1 attenuated SCG10 phosphorylation and delayed injury-induced axonal degeneration. Taken together, these data suggest that Spy1 is an important regulator of SCG10 and can be targeted in future axo-protective therapeutics.
authors: From the Medical College, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target.
authors: Yonghua
authors: Y
authors: Liu
authors: From the Medical College, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target.
authors: Youhua
authors: Y
authors: Wang
authors: From the Medical College, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target.
authors: Ying
authors: Y
authors: Chen
authors: From the Medical College, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target.
authors: Xiaohong
authors: X
authors: Li
authors: From the Medical College, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target.
authors: Jiao
authors: J
authors: Yang
authors: From the Medical College, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target.
authors: Yang
authors: Y
authors: Liu
authors: From the Medical College, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Jiangsu Province Key Laboratory of Neuroregeneration, and Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China shen_aiguo@yahoo.com.
authors: Aiguo
authors: A
authors: Shen
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D015723:Gene Library; D057809:HEK293 Cells; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008858:Microscopy, Phase-Contrast; D008868:Microtubule Proteins; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D025941:Protein Interaction Mapping; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries / Q000473:pathology; D050777:Stathmin; D020798:Two-Hybrid System Techniques
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D008565:Membrane Proteins; D008868:Microtubule Proteins; C486530:SPDYA protein, human; C063314:STMN2 protein, human; C582716:Spdya protein, rat; D050777:Stathmin; C512848:Stmn2 protein, rat; D048670:MAP Kinase Kinase 4
keywords: JNK; SCG10; Spy1; axon; axon loss; molecular cell biology; neurite outgrowth; neurodegenerative disease; phosphorylation; protein phosphorylation; protein stability; protein-protein interaction