The nuclear compartment is highly dynamic and its integrity is constantly challenged by mechanical forces. Transient nuclear envelope ruptures during interphase (NERDI) occur when mechanical stress is generated by cytoskeletal forces, and NERDI repair requires membrane remodelling activities to reseal the nucleus. However, for repair to be effective, mechanical strain imposed by the cytoskeleton needs to be relieved from the nucleus to counteract intranuclear pressure. Here we will combine cell biology, advanced microscopy and Atomic Force Microscopy/Magnetic Tweezers to reveal the molecular mechanisms that coordinate membrane remodelling with mechanical forces regulation to facilitate nuclear envelope repair and maintain genome stability.
The ESCRT machinery counteracts Nesprin-2G-mediated mechanical forces during nuclear envelope repair
Samuel S Wallis, Leandro N Ventimiglia, Evita Otigbah, Elvira Infante, Miguel Angel Cuesta-Geijo, Gururaj Rao Kidiyoor, M Alejandra Carbajal, Roland A Fleck, Marco Foiani, Sergi Garcia-Manyes, Juan Martin-Serrano* and Monica Agromayor*.
Under revision, Developmental Cell
The mechanical stability of proteins regulates their translocation rate into the cell nucleus.
Elvira Infante, Andrew Stannard, Stephanie J. Board, Palma Rico-Lastres, Elena Rostkova, Amy E. M. Beedle, Ainhoa Lezamiz, Yong Jian Wang, Samuel Gulaidi Breen, Fani Panagaki, Vinoth Sundar Rajan, Catherine Shanahan, Pere Roca-Cusachs & Sergi Garcia-Manyes. Nature Physics volume 15, pages 973–981 (2019).
CC2D1B Coordinates ESCRT-III Activity during the Mitotic Reformation of the Nuclear Envelope. Ventimiglia LN, Cuesta-Geijo MA, Martinelli N, Caballe A, Macheboeuf P, Miguet N, Parnham IM, Olmos Y, Carlton JG, Weissenhorn W, Martin-Serrano J. Dev Cell. 2018 Dec 3;47(5):547-563.
ESCRT machinery: Damage control at the nuclear membrane.Ventimiglia LN, Martin-Serrano J. Cell Res. 2016 Jun;26(6):641-2.