Non-muscle myosin IIB is critical for nuclear translocation during 3D invasion

J Cell Biol. 2015 Aug 17;210(4):583-94. doi: 10.1083/jcb.201502039. Epub 2015 Aug 10.

Abstract

Non-muscle myosin II (NMII) is reported to play multiple roles during cell migration and invasion. However, the exact biophysical roles of different NMII isoforms during these processes remain poorly understood. We analyzed the contributions of NMIIA and NMIIB in three-dimensional (3D) migration and in generating the forces required for efficient invasion by mammary gland carcinoma cells. Using traction force microscopy and microfluidic invasion devices, we demonstrated that NMIIA is critical for generating force during active protrusion, and NMIIB plays a major role in applying force on the nucleus to facilitate nuclear translocation through tight spaces. We further demonstrate that the nuclear membrane protein nesprin-2 is a possible linker coupling NMIIB-based force generation to nuclear translocation. Together, these data reveal a central biophysical role for NMIIB in nuclear translocation during 3D invasive migration, a result with relevance not only to cancer metastasis but for 3D migration in other settings such as embryonic cell migration and wound healing.

Publication types

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

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Biomechanical Phenomena
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Nucleus / physiology*
  • Mice
  • Nerve Tissue Proteins / metabolism
  • Nonmuscle Myosin Type IIB / physiology*
  • Nuclear Proteins / metabolism

Substances

  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Syne2 protein, mouse
  • Nonmuscle Myosin Type IIB