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Mechanobiology of Disease
Poster Abstracts
60
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.