title: CRMP1 Interacted with Spy1 During the Collapse of Growth Cones Induced by Sema3A and Acted on Regeneration After Sciatic Nerve Crush.
abstract: CRMP1, a member of the collapsin response mediator protein family (CRMPs), was reported to regulate axon outgrowth in Sema3A signaling pathways via interactions with its co-receptor protein neuropilin-1 and plexin-As through the Fyn-cyclin-dependent kinase 5 (CDK5) cascade and the sequential phosphorylation of CRMP1 by lycogen synthase kinase-3β (GSK-3β). Using yeast two-hybrid, we identified a new molecule, Speedy A1 (Spy1), a member of the Speedy/RINGO family, with an interaction with CRMP1. Besides, for the first time, we observed the association of CRMP1 with actin. Based on this, we wondered the association of them and their function in Sema3A-induced growth cones collapse and regeneration process after SNC. During our study, we constructed overexpression plasmid and short hairpin RNA (shRNA) to question the relationship of CRMP1/Spy1 and CRMP1/actin. We observed the interactions of CRMP1/Spy1 and CRMP1/actin. Besides, we found that Spy1 could affect CRMP1 phosphorylation actived by CDK5 and that enhanced CRMP1 phosphorylation might disturb the combination of CRMP1 and actin, which would contribute to abnormal of Sema3A-induced growth cones collapse and finally lead to influent regeneration process after rat sciatic nerve crush. Through rat walk footprint test, we also observed the variance during regeneration progress, respectively. We speculated that CRMP1 interacted with Spy1 which would disturb the association of CRMP1 with actin and was involved in the collapse of growth cones induced by Sema3A and regeneration after sciatic nerve crush.
authors.affiliation: Department of Orthopaedics, Affiliated Hospital of Nantong University and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, Jiangsu Province, 226001, People's Republic of China.|Department of Immunology, Medical College, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Yao
authors.affiliation: Department of Orthopaedics, Affiliated Hospital of Nantong University and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, Jiangsu Province, 226001, People's Republic of China.
authors.forename: Yong-Hua
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, Affiliated Hospital of Nantong University and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, Jiangsu Province, 226001, People's Republic of China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, Affiliated Hospital of Nantong University and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, Jiangsu Province, 226001, People's Republic of China.
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Ji
authors.affiliation: Department of Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, People's Republic of China.
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Yang
authors.affiliation: Department of Orthopaedics, Affiliated Hospital of Nantong University and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, Jiangsu Province, 226001, People's Republic of China.
authors.forename: Xian-Ting
authors.initials: XT
authors.lastname: Hang
authors.affiliation: Department of Orthopaedics, Affiliated Hospital of Nantong University and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, Jiangsu Province, 226001, People's Republic of China.
authors.forename: Zong-Mei
authors.initials: ZM
authors.lastname: Ding
authors.affiliation: Key Laboratory of Neuroregeneration, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, Affiliated Hospital of Nantong University and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, Jiangsu Province, 226001, People's Republic of China. wangyouhuantu@126.com.
authors.forename: You-Hua
authors.initials: YH
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, Affiliated Hospital of Nantong University and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, Jiangsu Province, 226001, People's Republic of China. CRMP1nt@163.com.
authors.forename: Ai-Guo
authors.initials: AG
authors.lastname: Shen
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D050505:Mutant Proteins / Q000378:metabolism; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D040121:Semaphorin-3A / Q000494:pharmacology*; D000098855:Collapsin Response Mediator Protein 1
chemical_list: D000199:Actins; D018797:Cell Cycle Proteins; D051360:Cyclin-Dependent Kinase 5; D050505:Mutant Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D040121:Semaphorin-3A; C102924:CRMP1 protein, human; D000098855:Collapsin Response Mediator Protein 1; C486530:SPDYA protein, human
keywords: Actin; CRMP1; Growth cones collapse; Sciatic nerve crush; Sema3A; Spy1