title: SCIRR39 promotes neurite extension via RhoA in NGF-induced PC12 cells.
abstract: SCIRR39 is an identified upregulated gene in rat primary neuron injury and/or regeneration process with roles largely unexplored. Using real-time quantitative PCR, Western blotting and immunofluorescence, SCIRR39 expression was detected in normal PC12 cells and upregulated in differentiated cells. The results of cell proliferation by Cell Counting Kit and cell cycle by flow cytometry indicated that SCIRR39 inhibited cell proliferation and induced the decrease in S phase. Importantly, immunofluorescent and RhoA pull-down assays showed that SCIRR39 strongly affected the neurite extension of NGF-treated PC12 cells through a RhoA-dependent mechanism, but the truncated mutants of SCIRR39 containing a truncation from 141AA to 211AA or from 397AA to 424AA failed to mock the SCIRR39 effect on neurite extension. Moreover, change of SCIRR39 expression in NGF-treated PC12 cells regulated the expression and phosphorylation of Fyn, a regulator of RhoA activity, but not the expression of ROCK II protein. Finally, immunofluorescence and RhoA pull-down assays revealed that obvious inhibition of neurite extension by SCIRR39 shRNA was reversed by RhoA inhibitor C3-transferase. Our results indicated that SCIRR39 increased the neurite extension in NGF-treated PC12 cells via RhoA, suggesting that SCIRR39 contributes to the regeneration of neuron injury by specifically altering the differentiation program.
authors.affiliation: State Key Laboratory of Proteomics, Department of Neurobiology, Institute of Basic Medical Sciences, The Academy of Military Medical Sciences, Beijing, PR China.
authors.forename: C F
authors.initials: CF
authors.lastname: Zhao
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: Y L
authors.initials: YL
authors.lastname: Ni
authors.forename: J W
authors.initials: JW
authors.lastname: Yang
authors.forename: H D
authors.initials: HD
authors.lastname: Hui
authors.forename: Z B
authors.initials: ZB
authors.lastname: Sun
authors.forename: S J
authors.initials: SJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D020932:Nerve Growth Factor / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C028666:Rnh1 protein, rat; D020932:Nerve Growth Factor; D020742:rhoA GTP-Binding Protein