title: Sema3F downregulates p53 expression leading to axonal growth cone collapse in primary hippocampal neurons.
abstract: Hippocampal nerve growth is regulated by the coordinated action of numerous external stimuli, including positively acting neurotrophin-derived growth cues and restrictive semaphorin cues, however the underlying cellular mechanisms remain largely unclear. We examined the potential cellular mechanism of Semaphorin3F (Sema3F) in cultured primary hippocampal neurons. We show that Sema3F can down-regulate p53 expression in primary hippocampal neurons, thereby contributing to growth cone collapse. Sema3F suppressed p53-induced pathways, which we show to be required to maintain growth cone structure. Sema3F-induced growth cone collapse was partially reversed by overexpression of p53, which promoted growth cone extension. Inhibition of p53 function by inhibitor, siRNAs, induced axonal growth cone collapse, whereas p53 over-expression led to larger growth cones in cultured primary hippocampal neurons.These data reveal a novel mechanism by which Sema3F can induce hippocampal neuron growth cone collapse and provide evidence for an intracellular mechanism for cross talk between positive and negative axon growth cues.
authors.affiliation: Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Guanglu
authors.initials: G
authors.lastname: Yang
authors.forename: Xiang
authors.initials: X
authors.lastname: Qu
authors.forename: Junmei
authors.initials: J
authors.lastname: Zhang
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhao
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000494:pharmacology; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D020868:Gene Silencing; D020439:Growth Cones / Q000187:drug effects* / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D020239:Receptor Cross-Talk / Q000187:drug effects; D014050:Toluene / Q000031:analogs & derivatives / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D052160:Benzothiazoles; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; C506913:Sema3F protein, rat; D016159:Tumor Suppressor Protein p53; D014050:Toluene; C121565:pifithrin