Active microtubule-actin cross-talk mediated by a nesprin-2G-kinesin complex

Sci Adv. 2025 Feb 21;11(8):eadq4726. doi: 10.1126/sciadv.adq4726. Epub 2025 Feb 21.

Abstract

Nesprin-2 Giant (N2G) is a large integral membrane protein that physically connects the nucleus to the cytoskeleton, but how N2G performs this activity to maintain nuclear positioning and drive nuclear movement is unclear. This study investigates N2G's role in nucleocytoskeletal coupling, a process critical for cellular function and development. We uncover multiple roles for N2G, including its activity as an F-actin bundler, an adapter that activates kinesin-1 motors, and a mediator of cytoskeletal cross-talk. Notably, N2G directly links kinesin-1 to F-actin, enabling the transport of actin filaments along microtubule tracks, establishing active cross-talk between the actin and microtubule cytoskeletons. These findings provide crucial insights into nuclear movement, advancing our understanding of fundamental cellular processes and their implications in development and disease.

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actins* / metabolism
  • Animals
  • Cell Nucleus / metabolism
  • Humans
  • Kinesins* / metabolism
  • Microfilament Proteins* / genetics
  • Microfilament Proteins* / metabolism
  • Microtubules* / metabolism
  • Nerve Tissue Proteins* / genetics
  • Nerve Tissue Proteins* / metabolism
  • Nuclear Proteins* / genetics
  • Nuclear Proteins* / metabolism
  • Protein Binding

Substances

  • Kinesins
  • Actins
  • Microfilament Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins