Stoichiometry controls activity of phase-separated clusters of actin signaling proteins

Lindsay B CaseMichael K Rosen


Biomolecular condensates concentrate macromolecules into foci without a surrounding membrane. Many condensates appear to form through multivalent interactions that drive liquid-liquid phase separation (LLPS). LLPS increases the specific activity of actin regulatory proteins toward actin assembly by the Arp2/3 complex. We show that this increase occurs because LLPS of the Nephrin-Nck-N-WASP signaling pathway on lipid bilayers increases membrane dwell time of N-WASP and Arp2/3 complex, consequently increasing actin assembly. Dwell time varies with relative stoichiometry of the signaling proteins in the phase-separated clusters, rendering N-WASP and Arp2/3 activity stoichiometry dependent. This mechanism of controlling protein activity is enabled by the stoichiometrically undefined nature of biomolecular condensates. Such regulation should be a general feature of signaling systems that assemble through multivalent interactions and drive nonequilibrium outputs.


Jan 1, 1982·Methods in Enzymology·J A Cooper, T D Pollard
Apr 17, 2003·Journal of the American Chemical Society·Tinglu YangPaul S Cremer
Nov 11, 2008·Molecular Cell·Shae B PadrickMichael K Rosen
Jun 17, 2011·Proceedings of the National Academy of Sciences of the United States of America·Shae B PadrickMichael K Rosen
May 23, 2012·The Journal of Cell Biology·Jonathon A DitlevBruce J Mayer
Aug 14, 2012·Proceedings of the National Academy of Sciences of the United States of America·Dongmyung OhJi Yu
Jan 8, 2013·Proceedings of the National Academy of Sciences of the United States of America·Benjamin A SmithJeff Gelles
Jul 23, 2013·Methods in Molecular Biology·Scott D HansenR Dyche Mullins
Jul 23, 2013·Methods in Molecular Biology·Lynda K DoolittleShae B Padrick
Aug 6, 2013·Nature Immunology·Angelo CastelloFacundo D Batista
Feb 13, 2015·ELife·Andrea PiccoMarko Kaksonen
Nov 11, 2015·Proceedings of the National Academy of Sciences of the United States of America·Sudeep BanjadeMichael K Rosen
Feb 4, 2016·Biophysical Journal·Paul J Michalski, Leslie M Loew
Jul 3, 2016·Proceedings of the National Academy of Sciences of the United States of America·William Y C HuangJay T Groves
Feb 23, 2017·Nature Reviews. Molecular Cell Biology·Salman F BananiMichael K Rosen
Sep 25, 2017·Science·Yongdae Shin, Clifford P Brangwynne
Aug 29, 2018·Proceedings of the National Academy of Sciences of the United States of America·Sofia Espinoza-SanchezThomas D Pollard

❮ Previous
Next ❯


Mar 29, 2019·Nature Reviews. Molecular Cell Biology·Paulina Strzyz
Sep 4, 2019·Journal of Cell Science·Priyanka KothariDouglas N Robinson
Oct 14, 2019·Traffic·Stephanie SpannlHyun O Lee
Dec 4, 2019·Nature Biotechnology·Dan BrachaClifford P Brangwynne
Oct 23, 2019·The Journal of Cell Biology·Johannes BaumgartJan Brugués
Nov 16, 2019·Cell Death & Disease·Anna RocchiFabio Benfenati
Feb 29, 2020·International Journal of Molecular Sciences·Sebastian Wolf
Feb 23, 2020·The FEBS Journal·Anna Bratek-SkickiPeter Tompa
Feb 15, 2020·The Journal of Pathology·Savvas Nikolaou, Laura M Machesky
Oct 24, 2019·Cellular and Molecular Life Sciences : CMLS·Bide ChenTizhong Shan
Oct 22, 2019·PLoS Computational Biology·Jeong-Mo ChoiRohit V Pappu
Jun 21, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sean M Cascarina, Eric D Ross
Aug 4, 2020·Emerging Topics in Life Sciences·Maria HondeleKarsten Weis
Aug 28, 2020·British Journal of Pharmacology·Wei WangQiaojun He
Mar 9, 2019·Science·Erik W Martin, Tanja Mittag
Jun 18, 2020·Science China. Life Sciences·Hong ZhangXueliang Zhu
Apr 6, 2019·Annual Review of Biophysics·Lindsay B CaseMichael K Rosen
Jun 25, 2020·Molecular Biology of the Cell·Huaiying ZhangMichael A Lampson
Oct 14, 2020·Emerging Topics in Life Sciences·Tina Wiegand, Anthony A Hyman
Oct 21, 2020·Emerging Topics in Life Sciences·Erik W Martin, Alex S Holehouse
Nov 11, 2020·Nature Reviews. Molecular Cell Biology·Andrew S LyonMichael K Rosen
Dec 11, 2020·Biochemical Society Transactions·Pinaki Swain, Stephanie C Weber
Jan 9, 2021·Cancer Cell·Ann BoijaRichard A Young
Jan 10, 2021·Journal of Cell Science·Ying Xie, Yansong Miao
Nov 11, 2020·The Journal of Biological Chemistry·Ameya P JalihalNils G Walter
Jan 19, 2021·Current Opinion in Cell Biology·Khuloud Jaqaman, Jonathon A Ditlev
Jan 3, 2021·Journal of Molecular Biology·Bede Portz, James Shorter
Jan 26, 2021·Current Opinion in Cell Biology·Shady Saad, Daniel F Jarosz
Jan 28, 2021·Current Opinion in Cell Biology·Brian G O'Flynn, Tanja Mittag
Jan 29, 2021·Molecular Biology of the Cell·Morgan L Pimm, Jessica L Henty-Ridilla
Oct 24, 2020·Nature Reviews. Molecular Cell Biology·Brian BelardiDaniel A Fletcher
Jan 8, 2021·Frontiers in Cell and Developmental Biology·Max KoppersGinny G Farías
Jan 19, 2021·Trends in Cell Biology·Chun SoMelina Schuh
Jan 24, 2021·Trends in Biochemical Sciences·Jeremy D SchmitMiroslav Dundr
Feb 14, 2021·Trends in Biochemical Sciences·Danfeng CaiJennifer Lippincott-Schwartz
Nov 4, 2020·ELife·Shan JiangBeidong Liu
Feb 13, 2021·Current Opinion in Cell Biology·Carla Garcia-Cabau, Xavier Salvatella

❮ Previous
Next ❯

Related Concepts

Related Feeds

Actin-binding Proteins

Actin-binding proteins are a component of the actin cytoskeleton that play essential roles in cellular functions such as regulation of actin polymerization, maintenance of cell polarity, gene expression regulation, cell motility and many more functions. Discover the latest research on actin-binding proteins here.