Biophysical Society Thematic Meeting | Singapore

Mechanobiology of Disease

Poster Abstracts

49-POS Board 49 Fimbrin Phosphorylation by Metaphase Cdk1 Regulates Actin Cable Dynamics in Budding Yeast Yansong Miao 4,3,1 , Xuemei Han 2 , Liangzhen Zheng 4 , Ying Xie 3 , Yuguang Mu 4 , John Yates 2 , David Drubin 1 . 4 Nanyang Technological University, School of Biological Sciences, Singapore, Singapore. 3 Nanyang Technological University, School of Chemical and Biomedical Engineering, Singapore, Singapore, 1 University of California, Berkeley, Berkeley, CA, USA, 2 The Scripps Research Institute, La Jolla, CA, USA, Dynamic assembly of actin cytoskeleton in distinct architectures, including branched and unbranched actin structures, is necessary for many biological processes in diverse eukaryotes. Unbranched actin cable is essential for intracellular membrane trafficking and polarized cell growth. 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 identified actin bundling protein fimbrin is phosphorylated by metaphase cyclin-dependent kinase (Cdk1) specifically in both in vitro and in vivo. Phosphorylation of fimbrin regulates its affinity to actin filaments. Based on 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. Sac6 is a fimbrin protein that belongs to an evolutionarily conserved protein family, which contains one EF-hand domain and two actin-binding domains for the cross-linking of actin filaments. Overall, this work identified fimbrin as a key target for cell cycle regulation of actin cable assembly in budding yeast, and suggested an underlying mechanism.

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