Our research at CIBSS aims at understanding the regulation and functions of the nuclear actin cytoskeleton in mammalian cells. We recently identified dynamic nuclear actin assembly during cell division. These actin filaments appear to facilitate nuclear growth and chromatin reorganisation, an essential process for proper genome organization and cell function during mitosis. Work in our laboratory aims at further elucidating the molecular players and mechanisms as well as the functional consequences for nuclear organization and cellular behavior.

We have further previously identified signal-regulated nuclear actin assembly through cell surface receptors. Currently, we are trying to elucidate the signaling events that promote rapid and transient nuclear actin polymerization that involves calcium elevations. Efforts in the laboratory try to decipher the intranuclear receptors and factors as well as the functional consequences of nuclear actin assembly for chromatin organization. In addition, we are studying the role of nuclear actin assembly during and for invasive cell migration. We approach these questions using high-resolution, live cell microscopy, optogenetics and biochemistry.

Keywords:

Actin cytoskeleton, nucleus, actin nucleation factors, nuclear shape, cancer cell invasion, chromatin

10 selected publications:

• Formin-mediated nuclear actin at androgen receptors promotes transcription.
  Knerr J, Werner R, Schwan C, Wang H, Gebhardt P, Grötsch H, Caliebe A, Spielmann M, Holterhus PM, Grosse R, Hornig NC.
  Nature. 2023 May;617(7961):616-622
• The Global Phosphorylation Landscape of SARS-CoV-2 Infection.
  Bouhaddou M, Memon D, Meyer B, White KM, Rezelj VV, Correa Marrero M, Polacco BJ, Melnyk JE, Ulferts S, Kaake RM, Batra J, Richards AL, Stevenson E, Gordon DE, Rojc A, Obernier K, Fabius JM, Soucheray M, Miorin L, Moreno E, Koh C, Tran QD, Hardy A, Robinot R, Vallet T, Nilsson-Payant BE, Hernandez-Armenta C, Dunham A, Weigang S, Knerr J, Modak M, Quintero D, Zhou Y, Dugourd A, Valdeolivas A, Patil T, Li Q, Hüttenhain R, Cakir M, Muralidharan M, Kim M, Jang G, Tutuncuoglu B, Hiatt J, Guo JZ, Xu J, Bouhaddou S, Mathy CJP, Gaulton A, Manners EJ, Félix E, Shi Y, Goff M, Lim JK, McBride T, O'Neal MC, Cai Y, Chang JCJ, Broadhurst DJ, Klippsten S, De Wit E, Leach AR, Kortemme T, Shoichet B, Ott M, Saez-Rodriguez J, tenOever BR, Mullins RD, Fischer ER, Kochs G, Grosse R, García-Sastre A, Vignuzzi M, Johnson JR, Shokat KM, Swaney DL, Beltrao P, Krogan NJ (2020).
  Cell. 182(3):685-712.e19.
• GPCR-induced calcium transients trigger nuclear actin assembly for chromatin dynamics.
  Wang Y, Sherrard A, Zhao B, Melak M, Trautwein J, Kleinschnitz EM, Tsopoulidis N, Fackler OT, Schwan C, Grosse R (2019).
  Nat Commun. 10(1):5271.
• A transient pool of nuclear F-actin at mitotic exit controls chromatin organization.br /> Baarlink C, Plessner M, Sherrard A, Morita K, Misu S, Virant D, Kleinschnitz EM, Harniman R, Alibhai D, Baumeister S, Miyamoto K, Endesfelder U, Kaidi A, Grosse R (2017).
  Nat Cell Biol. 19(12):1389-1399.
• MRTF transcription and Ezrin-dependent plasma membrane blebbing are required for entotic invasion.
  Hinojosa LS, Holst M, Baarlink C, Grosse R (2017).
  J Cell Biol. 216(10):3087-3095
• Junctional actin assembly is mediated by Formin-like 2 downstream of Rac1.
  Grikscheit K, Frank T, Wang Y, Grosse R (2015).
  J Cell Biol. 209(3):367-76.
• Formin-like 2 Promotes β1-Integrin Trafficking and Invasive Motility Downstream of PKCα.
  Wang Y, Arjonen A, Pouwels J, Ta H, Pausch P, Bange G, Engel U, Pan X, Fackler OT, Ivaska J, Grosse R (2015).
  Dev Cell. 34(4):475-83.
• Nuclear actin network assembly by formins regulates the SRF coactivator MAL.
  Baarlink C, Wang H, Grosse R (2013).
  Science. 340(6134):864-7
• SCAI acts as a suppressor of cancer cell invasion through the transcriptional control of beta1-integrin.
  Brandt DT, Baarlink C, Kitzing TM, Kremmer E, Ivaska J, Nollau P, Grosse R (2009).
  Nat Cell Biol. 11(5):557-68.
• Positive feedback between Dia1, LARG, and RhoA regulates cell morphology and invasion.
  Kitzing TM, Sahadevan AS, Brandt DT, Knieling H, Hannemann S, Fackler OT, Grosshans J, Grosse R (2007).
  Genes Dev. 21(12):1478-83.