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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
alpha-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.
