An actin-dependent annexin complex mediates plasma membrane repair in muscle

J Cell Biol. 2016 Jun 20;213(6):705-18. doi: 10.1083/jcb.201512022. Epub 2016 Jun 13.

Abstract

Disruption of the plasma membrane often accompanies cellular injury, and in muscle, plasma membrane resealing is essential for efficient recovery from injury. Muscle contraction, especially of lengthened muscle, disrupts the sarcolemma. To define the molecular machinery that directs repair, we applied laser wounding to live mammalian myofibers and assessed translocation of fluorescently tagged proteins using high-resolution microscopy. Within seconds of membrane disruption, annexins A1, A2, A5, and A6 formed a tight repair "cap." Actin was recruited to the site of damage, and annexin A6 cap formation was both actin dependent and Ca(2+) regulated. Repair proteins, including dysferlin, EHD1, EHD2, MG53, and BIN1, localized adjacent to the repair cap in a "shoulder" region enriched with phosphatidlyserine. Dye influx into muscle fibers lacking both dysferlin and the related protein myoferlin was substantially greater than control or individual null muscle fibers, underscoring the importance of shoulder-localized proteins. These data define the cap and shoulder as subdomains within the repair complex accumulating distinct and nonoverlapping components.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actins / metabolism*
  • Animals
  • Annexins / metabolism*
  • Calcium / metabolism
  • Cell Membrane / metabolism*
  • Cell Membrane / physiology*
  • Mice
  • Muscle Fibers, Skeletal / metabolism*
  • Muscle Fibers, Skeletal / physiology*
  • Protein Transport / physiology
  • Sarcolemma / metabolism
  • Wound Healing / physiology

Substances

  • Actins
  • Annexins
  • Calcium