Targeting of Nbp1 to the inner nuclear membrane is essential for spindle pole body duplication

EMBO J. 2011 Jul 22;30(16):3337-52. doi: 10.1038/emboj.2011.242.

Abstract

Spindle pole bodies (SPBs), like nuclear pore complexes, are embedded in the nuclear envelope (NE) at sites of fusion of the inner and outer nuclear membranes. A network of interacting proteins is required to insert a cytoplasmic SPB precursor into the NE. A central player of this network is Nbp1 that interacts with the conserved integral membrane protein Ndc1. Here, we establish that Nbp1 is a monotopic membrane protein that is essential for SPB insertion at the inner face of the NE. In vitro and in vivo studies identified an N-terminal amphipathic α-helix of Nbp1 as a membrane-binding element, with crucial functions in SPB duplication. The karyopherin Kap123 binds to a nuclear localization sequence next to this amphipathic α-helix and prevents unspecific tethering of Nbp1 to membranes. After transport into the nucleus, Nbp1 binds to the inner nuclear membrane. These data define the targeting pathway of a SPB component and suggest that the amphipathic α-helix of Nbp1 is important for SPB insertion into the NE from within the nucleus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / physiology*
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / physiology*
  • Cytoskeletal Proteins / chemistry
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / physiology*
  • Liposomes / metabolism
  • Membrane Fusion
  • Molecular Sequence Data
  • Nuclear Envelope / metabolism*
  • Nuclear Localization Signals
  • Nuclear Pore Complex Proteins / metabolism
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Phosphatidylcholines / metabolism
  • Protein Binding
  • Protein Interaction Mapping
  • Protein Structure, Secondary
  • Recombinant Fusion Proteins / physiology
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / physiology*
  • Sequence Deletion
  • Spindle Apparatus / metabolism*
  • Structure-Activity Relationship
  • beta Karyopherins / genetics
  • beta Karyopherins / physiology*

Substances

  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • Kap123 protein, S cerevisiae
  • Liposomes
  • NBP1 protein, S cerevisiae
  • NDC1 protein, S cerevisiae
  • Nuclear Localization Signals
  • Nuclear Pore Complex Proteins
  • Nuclear Proteins
  • Phosphatidylcholines
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • beta Karyopherins