title: A link between the nuclear-localized srGAP3 and the SWI/SNF chromatin remodeler Brg1.
abstract: The Slit-Robo GTPase activating protein 3 (srGAP3) is an important modulator of actin cytoskeletal dynamics and has an important influence on a variety of neurodevelopmental processes. Mutations in the SRGAP3 gene on chromosome 3p25 have been found in patients with intellectual disability. Genome-wide association studies and behavioral assays of knockout mice had also revealed SRGAP3 as a risk gene for schizophrenia. We have recently shown that srGAP3 protein undergoes regulated shuttling between the cytoplasm and the nucleus during neuronal development. It is shown here that nuclear-localized srGAP3 interacts with the SWI/SNF remodeling factor Brg1. This interaction is mediated by the C-terminal of srGAP3 and the ATPase motif of Brg1. In the primary cultured rat cortical neurons, the levels of nuclear-localized srGAP3 and its interaction with Brg1 have a significant impact on dendrite complexity. Furthermore, the interaction between srGAP3 and Brg1 was also involved in valproic acid (VPA) -induced neuronal differentiation of Neuro2a cells. We then show that GTP-bound Rac1 and GAP-43 may be potential mediators of nuclear srGAP3 and Brg1. Our results not only indicate a novel signaling pathway that contributes to neuronal differentiation and dendrite morphology, but also implicate a novel molecular mechanism underlying srGAP3 regulation of gene expression.
authors.affiliation: School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Yun-Kai
authors.initials: YK
authors.lastname: Dai
authors.affiliation: School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China; Institute of Nano-Biomedicine and Engineering, Bio-X Center, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Ma
authors.affiliation: School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Keng
authors.initials: K
authors.lastname: Chen
authors.affiliation: School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Ya-Jing
authors.initials: YJ
authors.lastname: Mi
authors.affiliation: Institute of Nano-Biomedicine and Engineering, Bio-X Center, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Hua-Lin
authors.initials: HL
authors.lastname: Fu
authors.affiliation: Institute of Nano-Biomedicine and Engineering, Bio-X Center, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Da-Xiang
authors.initials: DX
authors.lastname: Cui
authors.affiliation: School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China; Institute of Nano-Biomedicine and Engineering, Bio-X Center, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: weilinjin@yahoo.com.
authors.forename: Wei-Lin
authors.initials: WL
authors.lastname: Jin
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D042002:Chromatin Assembly and Disassembly; D004265:DNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019922:GAP-43 Protein / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014635:Valproic Acid / Q000494:pharmacology; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D019922:GAP-43 Protein; D020690:GTPase-Activating Proteins; D009687:Nuclear Proteins; C465659:SRGAP3 protein, human; D014157:Transcription Factors; D014635:Valproic Acid; C578929:Smarca4 protein, rat; D004265:DNA Helicases; D020830:rac1 GTP-Binding Protein
keywords: Brg1; Chromatin remodeling; GAP-43; Neuronal differentiation; Rac1; srGAP3