A mechanosensory system governs myosin II accumulation in dividing cells

Mol Biol Cell. 2012 Apr;23(8):1510-23. doi: 10.1091/mbc.E11-07-0601. Epub 2012 Feb 29.

Abstract

The mitotic spindle is generally considered the initiator of furrow ingression. However, recent studies suggest that furrows can form without spindles, particularly during asymmetric cell division. In Dictyostelium, the mechanoenzyme myosin II and the actin cross-linker cortexillin I form a mechanosensor that responds to mechanical stress, which could account for spindle-independent contractile protein recruitment. Here we show that the regulatory and contractility network composed of myosin II, cortexillin I, IQGAP2, kinesin-6 (kif12), and inner centromeric protein (INCENP) is a mechanical stress-responsive system. Myosin II and cortexillin I form the core mechanosensor, and mechanotransduction is mediated by IQGAP2 to kif12 and INCENP. In addition, IQGAP2 is antagonized by IQGAP1 to modulate the mechanoresponsiveness of the system, suggesting a possible mechanism for discriminating between mechanical and biochemical inputs. Furthermore, IQGAP2 is important for maintaining spindle morphology and kif12 and myosin II cleavage furrow recruitment. Cortexillin II is not directly involved in myosin II mechanosensitive accumulation, but without cortexillin I, cortexillin II's role in membrane-cortex attachment is revealed. Finally, the mitotic spindle is dispensable for the system. Overall, this mechanosensory system is structured like a control system characterized by mechanochemical feedback loops that regulate myosin II localization at sites of mechanical stress and the cleavage furrow.

Publication types

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

MeSH terms

  • Cell Division*
  • Chromosomal Proteins, Non-Histone / metabolism
  • Dictyostelium / cytology*
  • Dictyostelium / metabolism*
  • Kinesin / metabolism*
  • Mechanotransduction, Cellular
  • Microfilament Proteins / metabolism*
  • Myosin Type II / metabolism*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*
  • Spindle Apparatus / metabolism
  • Spindle Apparatus / physiology
  • Stress, Physiological
  • ras GTPase-Activating Proteins / metabolism*

Substances

  • Chromosomal Proteins, Non-Histone
  • Microfilament Proteins
  • Protozoan Proteins
  • ctxA protein, Dictyostelium discoideum
  • ras GTPase-Activating Proteins
  • Myosin Type II
  • Kinesin