On the inscrutable role of Inscuteable: structural basis and functional implications for the competitive binding of NuMA and Inscuteable to LGN

Open Biol. 2012 Aug;2(8):120102. doi: 10.1098/rsob.120102.

Abstract

Alignment of the mitotic spindle to the cellular polarity axis is a prerequisite for asymmetric cell divisions. The protein network coordinating the spindle position with cortical polarity includes the molecular machinery pulling on astral microtubules, which is assembled on conserved NuMA:LGN:Gαi complexes, the polarity proteins Par3:Par6:aPKC and an adaptor molecule known as Inscuteable (Insc). To date, all these components were assumed to enter a macromolecular complex localized at polarity sites in mitosis. However, recent structural studies revealed the Insc and NuMA are mutually exclusive interactors of LGN, implying that the molecular mechanism of spindle coupling to polarity is more sophisticated than has been believed to date.

Keywords: asymmetric cell division; spindle orientation; structural biology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Antigens, Nuclear / chemistry
  • Antigens, Nuclear / metabolism*
  • Binding, Competitive
  • Cell Cycle Proteins
  • Humans
  • Intracellular Signaling Peptides and Proteins / chemistry
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mitosis
  • Models, Molecular
  • Nuclear Matrix-Associated Proteins / chemistry
  • Nuclear Matrix-Associated Proteins / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • Spindle Apparatus / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, Nuclear
  • Cell Cycle Proteins
  • GPSM2 protein, human
  • Insc protein, human
  • Intracellular Signaling Peptides and Proteins
  • NUMA1 protein, human
  • Nuclear Matrix-Associated Proteins