气候变化领域集成服务门户(CCPortal): Drebrin regulates cytoskeleton dynamics in migrating neurons through interaction with CXCR4

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DOI	10.1073/pnas.2009493118
	Drebrin regulates cytoskeleton dynamics in migrating neurons through interaction with CXCR4
	Shan Y.; Farmer S.M.; Wray S.
发表日期	2021
ISSN	00278424
卷号	118 期号:3
英文摘要	Stromal cell-derived factor-1 (SDF-1) and chemokine receptor type 4 (CXCR4) are regulators of neuronal migration (e.g., GnRH neurons, cortical neurons, and hippocampal granule cells). However, how SDF-1/CXCR4 alters cytoskeletal components remains unclear. Developmentally regulated brain protein (drebrin) stabilizes actin polymerization, interacts with microtubule plus ends, and has been proposed to directly interact with CXCR4 in T cells. The current study examined, in mice, whether CXCR4 under SDF-1 stimulation interacts with drebrin to facilitate neuronal migration. Bioinformatic prediction of protein–protein interaction highlighted binding sites between drebrin and crystallized CXCR4. In migrating GnRH neurons, drebrin, CXCR4, and the microtubule plus-end binding protein EB1 were localized close to the cell membrane. Coimmunoprecipitation (co-IP) confirmed a direct interaction between drebrin and CXCR4 using wild-type E14.5 whole head and a GnRH cell line. Analysis of drebrin knockout (DBN1 KO) mice showed delayed migration of GnRH cells into the brain. A decrease in hippocampal granule cells was also detected, and co-IP confirmed a direct interaction between drebrin and CXCR4 in PN4 hippocampi. Migration assays on primary neurons established that inhibiting drebrin (either pharmacologically or using cells from DBN1 KO mice) prevented the effects of SDF-1 on neuronal movement. Bioinformatic prediction then identified binding sites between drebrin and the microtubule plus end protein, EB1, and super-resolution microscopy revealed decreased EB1 and drebrin coexpression after drebrin inhibition. Together, these data show a mechanism by which a chemokine, via a membrane receptor, communicates with the intracellular cytoskeleton in migrating neurons during central nervous system development. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Neuronal migration \| drebrin \| CXCR4 \| GnRH \| hippocampus
语种	英语
scopus关键词	binding protein; chemokine receptor CXCR4; drebrin; microtubule plus end binding protein EB1; stromal cell derived factor 1; unclassified drug; actin filament; adult; animal cell; animal tissue; Article; binding affinity; binding site; bioinformatics; carboxy terminal sequence; cell membrane; cell migration; central nervous system; controlled study; cytoskeleton; dentate gyrus granular layer; embryo; female; granule cell; hippocampus; immunoprecipitation; knockout mouse; microtubule; mouse; nerve cell; nervous system development; nonhuman; priority journal; protein expression; protein localization; protein protein interaction
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180950
作者单位	Cellular and Developmental Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, United States
推荐引用方式 GB/T 7714	Shan Y.,Farmer S.M.,Wray S.. Drebrin regulates cytoskeleton dynamics in migrating neurons through interaction with CXCR4[J],2021,118(3).
APA	Shan Y.,Farmer S.M.,&Wray S..(2021).Drebrin regulates cytoskeleton dynamics in migrating neurons through interaction with CXCR4.Proceedings of the National Academy of Sciences of the United States of America,118(3).
MLA	Shan Y.,et al."Drebrin regulates cytoskeleton dynamics in migrating neurons through interaction with CXCR4".Proceedings of the National Academy of Sciences of the United States of America 118.3(2021).