LGN/mInsc and LGN/NuMA complex structures suggest distinct functions in asymmetric cell division for the Par3/mInsc/LGN and Gαi/LGN/NuMA pathways

Mol Cell. 2011 Aug 5;43(3):418-31. doi: 10.1016/j.molcel.2011.07.011.

Abstract

Asymmetric cell division requires the establishment of cortical cell polarity and the orientation of the mitotic spindle along the axis of cell polarity. Evidence from invertebrates demonstrates that the Par3/Par6/aPKC and NuMA/LGN/Gαi complexes, which are thought to be physically linked by the adaptor protein mInscuteable (mInsc), play indispensable roles in this process. However, the molecular basis for the binding of LGN to NuMA and mInsc is poorly understood. The high-resolution structures of the LGN/NuMA and LGN/mInsc complexes presented here provide mechanistic insights into the distinct and highly specific interactions of the LGN TPRs with mInsc and NuMA. Structural comparisons, together with biochemical and cell biology studies, demonstrate that the interactions of NuMA and mInsc with LGN are mutually exclusive, with mInsc binding preferentially. Our results suggest that the Par3/mInsc/LGN and NuMA/LGN/Gαi complexes play sequential and partially overlapping roles in asymmetric cell division.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antigens, Nuclear / chemistry*
  • Antigens, Nuclear / genetics
  • Antigens, Nuclear / physiology
  • Carrier Proteins / chemistry*
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology
  • Cell Adhesion Molecules / chemistry
  • Cell Adhesion Molecules / metabolism
  • Cell Adhesion Molecules / physiology
  • Cell Cycle Proteins / chemistry*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / physiology
  • Cell Division / physiology*
  • Cell Polarity
  • Crystallography, X-Ray
  • Escherichia coli / genetics
  • GTP-Binding Protein alpha Subunit, Gi2 / chemistry
  • GTP-Binding Protein alpha Subunit, Gi2 / metabolism
  • GTP-Binding Protein alpha Subunit, Gi2 / physiology
  • Humans
  • Mice
  • Models, Molecular
  • Mutagenesis
  • Nuclear Matrix-Associated Proteins / chemistry*
  • Nuclear Matrix-Associated Proteins / genetics
  • Nuclear Matrix-Associated Proteins / physiology
  • Protein Structure, Tertiary
  • Protein Transport
  • Spindle Apparatus / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, Nuclear
  • Carrier Proteins
  • Cell Adhesion Molecules
  • Cell Cycle Proteins
  • LGN protein, mouse
  • NUMA1 protein, human
  • Nuclear Matrix-Associated Proteins
  • Pard3 protein, mouse
  • inscuteable protein, mouse
  • GTP-Binding Protein alpha Subunit, Gi2

Associated data

  • PDB/3RO2
  • PDB/3RO3