title: Class 3 semaphorin mediates dendrite growth in adult newborn neurons through Cdk5/FAK pathway.
abstract: Class 3 semaphorins are well-known axonal guidance cues during the embryonic development of mammalian nervous system. However, their activity on postnatally differentiated neurons in neurogenic regions of adult brains has not been characterized. We found that silencing of semaphorin receptors neuropilins (NRP) 1 or 2 in neural progenitors at the adult mouse dentate gyrus resulted in newly differentiated neurons with shorter dendrites and simpler branching in vivo. Tyrosine phosphorylation (Tyr 397) and serine phosphorylation (Ser 732) of FAK were essential for these effects. Semaphorin 3A and 3F mediate serine phosphorylation of FAK through the activation of Cdk5. Silencing of either Cdk5 or FAK in newborn neurons phenocopied the defects in dendritic development seen upon silencing of NRP1 or NRP2. Furthermore, in vivo overexpression of Cdk5 or FAK rescued the dendritic phenotypes seen in NRP1 and NRP2 deficient neurons. These results point to a novel role for class 3 semaphorins in promoting dendritic growth and branching during adult hippocampal neurogenesis through the activation of Cdk5-FAK signaling pathway.
authors.affiliation: Program in Neuroscience and Behavioral Disorder, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Teclise
authors.initials: T
authors.lastname: Ng
authors.forename: Jae Ryun
authors.initials: JR
authors.lastname: Ryu
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Sohn
authors.forename: Terence
authors.initials: T
authors.lastname: Tan
authors.forename: Hongjun
authors.initials: H
authors.lastname: Song
authors.forename: Guo-Li
authors.initials: GL
authors.lastname: Ming
authors.forename: Eyleen L K
authors.initials: EL
authors.lastname: Goh
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D051360:Cyclin-Dependent Kinase 5 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D003712:Dendrites / Q000187:drug effects / Q000502:physiology*; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D039942:Neuropilin-1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D039943:Neuropilin-2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D011687:Purines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012190:Retroviridae / Q000235:genetics; D000077546:Roscovitine; D039961:Semaphorins / Q000494:pharmacology*; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D039943:Neuropilin-2; D011687:Purines; D034741:RNA, Small Interfering; D039961:Semaphorins; D042461:Vascular Endothelial Growth Factor A; D000077546:Roscovitine; D039942:Neuropilin-1; D014443:Tyrosine; D012694:Serine; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051360:Cyclin-Dependent Kinase 5; D000469:Alkaline Phosphatase