title: Spectraplakin Induces Positive Feedback between Fusogens and the Actin Cytoskeleton to Promote Cell-Cell Fusion.
abstract: Cell-cell fusion generally requires cellular fusogenic proteins and actin-propelled membrane protrusions. However, the molecular connections between fusogens and the actin cytoskeleton remain unclear. Here, we show that the Caenorhabditis elegans fusogen EFF-1 and F-actin are enriched at the cortex of the post-embryonic fusing cells, and conditional mutations of WASP and Arp2/3 delay cell-cell fusion by impairing EFF-1 localization. Our affinity purification and mass spectrometry analyses determined that an actin-binding protein, spectraplakin/VAB-10A, binds to EFF-1. VAB-10A promotes cell-cell fusion by linking EFF-1 to the actin cytoskeleton. Conversely, EFF-1 enhanced the F-actin bundling activity of VAB-10A in vitro, and actin dynamics in the cortex were reduced in eff-1 or vab-10a mutants. Thus, cell-cell fusion is promoted by a positive feedback loop in which actin filaments that are crosslinked by spectraplakin to recruit fusogens to fusion sites are reinforced via fusogens, thereby increasing the probability of further fusogen accumulation to form fusion synapses.
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Life Sciences and MOE Key Laboratory for Protein Science, Tsinghua University, Beijing 100084, China.
authors.forename: Yihong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Life Sciences and MOE Key Laboratory for Protein Science, Tsinghua University, Beijing 100084, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: National Institute of Biological Science, Beijing 102206, China.
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Li
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Life Sciences and MOE Key Laboratory for Protein Science, Tsinghua University, Beijing 100084, China.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Life Sciences and MOE Key Laboratory for Protein Science, Tsinghua University, Beijing 100084, China.
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Life Sciences and MOE Key Laboratory for Protein Science, Tsinghua University, Beijing 100084, China.
authors.forename: Huifang
authors.initials: H
authors.lastname: Hu
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Life Sciences and MOE Key Laboratory for Protein Science, Tsinghua University, Beijing 100084, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Life Sciences and MOE Key Laboratory for Protein Science, Tsinghua University, Beijing 100084, China.
authors.forename: Jia-Wei
authors.initials: JW
authors.lastname: Wu
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Life Sciences and MOE Key Laboratory for Protein Science, Tsinghua University, Beijing 100084, China.
authors.forename: Zhi-Xin
authors.initials: ZX
authors.lastname: Wang
authors.affiliation: National Institute of Biological Science, Beijing 102206, China.
authors.forename: Meng-Qiu
authors.initials: MQ
authors.lastname: Dong
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Life Sciences and MOE Key Laboratory for Protein Science, Tsinghua University, Beijing 100084, China.
authors.forename: Shanjin
authors.initials: S
authors.lastname: Huang
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Life Sciences and MOE Key Laboratory for Protein Science, Tsinghua University, Beijing 100084, China. Electronic address: guangshuoou@tsinghua.edu.cn.
authors.forename: Guangshuo
authors.initials: G
authors.lastname: Ou
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D051376:Actin-Related Protein 2-3 Complex; D000199:Actins / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002459:Cell Fusion; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D025461:Feedback, Physiological; D007814:Larva / Q000166:cytology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D011485:Protein Binding; D055550:Protein Stability; D021381:Protein Transport; D051316:Wiskott-Aldrich Syndrome Protein
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D029742:Caenorhabditis elegans Proteins; C470734:EFF-1 protein, C elegans; D008562:Membrane Glycoproteins; C475260:VAB-10 protein, C elegans; D051316:Wiskott-Aldrich Syndrome Protein
keywords: actin; cell-cell fusion; fusogens; spectraplakin