BAF facilitates interphase nuclear membrane repair through recruitment of nuclear transmembrane proteins

Mol Biol Cell. 2020 Jul 15;31(15):1551-1560. doi: 10.1091/mbc.E20-01-0009. Epub 2020 May 27.

Abstract

Nuclear membrane rupture during interphase occurs in a variety of cell contexts, both healthy and pathological. Membrane ruptures can be rapidly repaired, but these mechanisms are still unclear. Here we show barrier-to-autointegration factor (BAF), a nuclear envelope protein that shapes chromatin and recruits membrane proteins in mitosis, also facilitates nuclear membrane repair in interphase, in part through recruitment of the nuclear membrane proteins emerin and Lem-domain-containing protein 2 (LEMD2) to rupture sites. Characterization of GFP-BAF accumulation at nuclear membrane rupture sites confirmed BAF is a fast, accurate, and persistent mark of nucleus rupture whose kinetics are partially dictated by membrane resealing. BAF depletion significantly delayed nuclear membrane repair, with a larger effect on longer ruptures. This phenotype could be rescued by GFP-BAF, but not by a BAF mutant lacking the Lap2, emerin, Man1 (LEM)-protein binding domain. Depletion of the BAF interactors LEMD2 or emerin, and to a lesser extent lamin A/C, increased the duration of nucleus ruptures, consistent with LEM-protein binding being a key function of BAF during membrane repair. Overall our results suggest a model where BAF is critical for timely repair of large ruptures in the nuclear membrane, potentially by facilitating membrane attachment to the rupture site.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • DNA-Binding Proteins / metabolism*
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Interphase*
  • Kinetics
  • Lamin Type A / metabolism
  • Membrane Proteins / metabolism*
  • Nuclear Envelope / metabolism*
  • Nuclear Proteins / metabolism*
  • Protein Binding

Substances

  • BANF1 protein, human
  • DNA-Binding Proteins
  • Lamin Type A
  • Membrane Proteins
  • Nuclear Proteins
  • emerin
  • Green Fluorescent Proteins