A link between the nuclear-localized srGAP3 and the SWI/SNF chromatin remodeler Brg1

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• 作者：Yun-Kai Dai^a ; ¹ ; Yue Ma^a ; ^b ; ¹ ; Keng Chen^a ; ¹ ; ² ; Ya-Jing Mi^a ; Hua-Lin Fu^b ; Da-Xiang Cui^b ; Wei-Lin Jin^a ; ^b ; ^{weilinjin@yahoo.com" class="auth_mail} ; ^{weilinjin@sjtu.edu.cn" class="auth_mail}
• 关键词：BAF ; Brg1 Brm associated factors ; Brg1 ; Brahma-related gene 1 ; Brm ; Brahma ; CC ; Coiled-coil ; CDC42 ; Cell division control protein 42 homolog ; DN ; Dominant Negative ; E ; embryonic ; EGFP ; enhanced green fluorescent protein ; F-BAR ; FCH-Bin/Amphiphysin/Rvs ; FCH ; Fer ; Fes CIP4 homology ; GAP-43 ; Growth associated protein-43 ; GAPDH ; Glyceraldehyde 3-phosphate dehydrogenase ; GST ; glutathione S-transferase ; MEGAP ; Mental disorder-associated GAP ; P ; postnatal ; Rac1 ; Ras-related C3 botulinum toxin substrate
• 刊名：Molecular and Cellular Neuroscience
• 出版年：May 2014
• 年：2014
• 卷：60
• 期：Complete
• 页码：10-25
• 全文大小：2758 K

文摘

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.