title: Fimbrin phosphorylation by metaphase Cdk1 regulates actin cable dynamics in budding yeast.
abstract: Actin cables, composed of actin filament bundles nucleated by formins, mediate intracellular transport for cell polarity establishment and maintenance. We previously observed that metaphase cells preferentially promote actin cable assembly through cyclin-dependent kinase 1 (Cdk1) activity. However, the relevant metaphase Cdk1 targets were not known. Here we show that the highly conserved actin filament crosslinking protein fimbrin is a critical Cdk1 target for actin cable assembly regulation in budding yeast. Fimbrin is specifically phosphorylated on threonine 103 by the metaphase cyclin-Cdk1 complex, in vivo and in vitro. On the basis of conformational simulations, we suggest that this phosphorylation stabilizes fimbrin's N-terminal domain, and modulates actin filament binding to regulate actin cable assembly and stability in cells. Overall, this work identifies fimbrin as a key target for cell cycle regulation of actin cable assembly in budding yeast, and suggests an underlying mechanism.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3202, USA.|School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore.|School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459, Singapore.
authors.forename: Yansong
authors.initials: Y
authors.lastname: Miao
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Han
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore.
authors.forename: Liangzhen
authors.initials: L
authors.lastname: Zheng
authors.affiliation: School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459, Singapore.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xie
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore.
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Mu
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: John R
authors.identifier: http://orcid.org/0000-0001-5267-1672
authors.initials: JR
authors.lastname: Yates
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3202, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Drubin
mesh_terms: D000199:Actins / Q000378:metabolism*; D016203:CDC2 Protein Kinase / Q000737:chemistry / Q000378:metabolism*; D003198:Computer Simulation; D016213:Cyclins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008677:Metaphase; D008840:Microfilament Proteins / Q000378:metabolism*; D009154:Mutation; D010766:Phosphorylation; D010769:Phosphothreonine / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D004718:Saccharomycetales / Q000166:cytology* / Q000201:enzymology*
chemical_list: D000199:Actins; D016213:Cyclins; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D029701:Saccharomyces cerevisiae Proteins; C026742:plastin; D010769:Phosphothreonine; D016203:CDC2 Protein Kinase