To grow, divide, signal, move and withstand pressure, eukaryotic cells dynamically rearrange their actin cytoskeleton. The formin family of proteins nucleates and directs the elongation of unbranched actin filaments that are incorporated into cytokinetic contractile rings, filopodia and stress fibers. Most eukaryotes express multiple formin isoforms, which possess specific activities that make them uniquely suited to fulfill a particular role in the cell. Although the three formin isoforms in fission yeast each have a distinct biological function (cytokinesis, interphase cable assembly, mating), the functions of the 15 mammalian formins are far from clear. Because we lack many of the details required to understand how formins function in cells, it is not known how these proteins promote normal cellular proliferation. The Courtemanche lab aims to understand formin-mediated actin assembly using single-molecule fluorescence microscopy, spectroscopy and thermodynamic modeling. Current projects in the lab focus on addressing several questions: How do formins nucleate filaments? How do formin-bound filaments interact with other actin-binding proteins? How do sequence variations confer unique properties to formin orthologs? How do formins cooperate to polymerize bundled filaments? How do formins respond to force?
Selected Publications: PubMed
Courtemanche N. Mechanisms of formin-mediated actin assembly and dynamics. Biophys Rev. 2018 Nov 3. doi: 10.1007/s12551-018-0468-6. [Epub ahead of print] Review. PubMed PMID: 30392063.
Fujiwara I, Zweifel ME, Courtemanche N, Pollard TD. Latrunculin A Accelerates Actin Filament Depolymerization in Addition to Sequestering Actin Monomers. Curr Biol. 2018 Oct 8;28(19):3183-3192.e2. doi: 10.1016/j.cub.2018.07.082. Epub 2018 Sep 27. PubMed PMID: 30270183; PubMed Central PMCID: PMC6179359.
Sherer LA, Zweifel ME, Courtemanche N. Dissection of two parallel pathways for formin-mediated actin filament elongation. J Biol Chem. 2018 Sep 28. pii: jbc.RA118.004845. doi: 10.1074/jbc.RA118.004845. [Epub ahead of print] PubMed PMID: 30266808.
Aydin F, Courtemanche N, Pollard TD, Voth GA. Gating mechanisms during actin filament elongation by formins. Elife. 2018 Jul 23;7. pii: e37342. doi: 10.7554/eLife.37342. PubMed PMID: 30035712; PubMed Central PMCID: PMC6056239. p>Courtemanche N, Pollard TD, Chen Q. Avoiding artefacts when counting polymerized actin in live cells with LifeAct fused to fluorescent proteins. Nat Cell Biol. 2016 Jun;18(6):676-83. doi: 10.1038/ncb3351. Epub 2016 May 9. PubMed PMID: 27159499; PubMed Central PMCID: PMC5509211.
Baker JL*, Courtemanche N*, Parton DL*, McCullagh M, Pollard TD, Voth GA. (2015) Electrostatic interactions between the Bni1p Formin FH2 domain and actin influence actin filament nucleation. Structure. Jan 6;23(1):68-79
Courtemanche N, Pollard TD. (2013) Interaction of profilin with the barbed end of actin filaments. Biochemistry. Sep 17;52(37):6456-66.
Courtemanche N, Lee JY, Pollard TD, Greene EC. (2013) Tension modulates actin filament polymerization mediated by formin and profilin. Proc Natl Acad Sci U S A. Jun 11;110(24):9752-7.
Courtemanche N, Pollard TD. (2012) Determinants of Formin Homology 1 (FH1) domain function in actin filament elongation by formins. J Biol Chem. Mar 2;287(10):7812-20.
Courtemanche N, Barrick D. (2008) The leucine-rich repeat domain of Internalin B folds along a polarized N-terminal pathway. Structure. May;16(5):705-14.
Courtemanche N, Barrick D. (2008) Folding thermodynamics and kinetics of the leucine-rich repeat domain of the virulence factor Internalin B. Protein Sci. Jan;17(1):43-53.