Postmitotic expansion of cell nuclei requires nuclear actin filament bundling by α‐actinin 4. (22nd September 2020)

• Record Type: Journal Article
• Authors: Krippner, Sylvia; Winkelmeier, Jannik; Knerr, Julian; Brandt, Dominique T; Virant, David; Schwan, Carsten; Endesfelder, Ulrike; Grosse, Robert
• Is Part Of: EMBO reports. Volume 21:Number 11(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-09-22
• Subjects: actin bundling -- chromatin -- mitosis -- nuclear actin -- nuclear expansion; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.202050758
• Languages: English
• ISSNs: 1469-221X

Abstract

Abstract: The actin cytoskeleton operates in a multitude of cellular processes including cell shape and migration, mechanoregulation, and membrane or organelle dynamics. However, its filamentous properties and functions inside the mammalian cell nucleus are less well explored. We previously described transient actin assembly at mitotic exit that promotes nuclear expansion during chromatin decondensation. Here, we identify non‐muscle α‐actinin 4 (ACTN4) as a critical regulator to facilitate F‐actin reorganization and bundling during postmitotic nuclear expansion. ACTN4 binds to nuclear actin filament structures, and ACTN4 clusters associate with nuclear F‐actin in a highly dynamic fashion. ACTN4 but not ACTN1 is required for proper postmitotic nuclear volume expansion, mediated by its actin‐binding domain. Using super‐resolution imaging to quantify actin filament numbers and widths in individual nuclei, we find that ACTN4 is necessary for postmitotic nuclear actin reorganization and actin filament bundling. Our findings uncover a nuclear cytoskeletal function for ACTN4 to control nuclear size and chromatin organization during mitotic cell division. Synopsis: Alpha‐actinin‐4 (ACTN4) dynamically associates with and bundles nuclear actin filaments to control the growth of daughter cell nuclei after mitotic cell division to promote chromatin reorganization. ACTN4 organizes actin filaments into higher order bundles inside the nuclear compartment of mammalian cells. ACTN4 promotes nuclear expansion and chromatin decondensation at mitotic exit dependent on its actin binding calponin‐homology‐1 (CH1) domain. Live cell imaging reveals that nuclear ACTN4 is mobile and highly dynamic. Abstract : Alpha‐actinin‐4 (ACTN4) dynamically associates with and bundles nuclear actin filaments to control the growth of daughter cell nuclei after mitotic cell division to promote chromatin reorganization.