LAB-1 antagonizes the Aurora B kinase in C. elegans

Genes Dev. 2008 Oct 15;22(20):2869-85. doi: 10.1101/gad.1691208.

Abstract

The Shugoshin/Aurora circuitry that controls the timely release of cohesins from sister chromatids in meiosis and mitosis is widely conserved among eukaryotes, although little is known about its function in organisms whose chromosomes lack a localized centromere. Here we show that Caenorhabditis elegans chromosomes rely on an alternative mechanism to protect meiotic cohesin that is shugoshin-independent and instead involves the activity of a new chromosome-associated protein named LAB-1 (Long Arm of the Bivalent). LAB-1 preserves meiotic sister chromatid cohesion by restricting the localization of the C. elegans Aurora B kinase, AIR-2, to the interface between homologs via the activity of the PP1/Glc7 phosphatase GSP-2. The localization of LAB-1 to chromosomes of dividing embryos and the suppression of mitotic-specific defects in air-2 mutant embryos with reduced LAB-1 activity support a global role of LAB-1 in antagonizing AIR-2 in both meiosis and mitosis. Although the localization of a GFP fusion and the analysis of mutants and RNAi-mediated knockdowns downplay a role for the C. elegans shugoshin protein in cohesin protection, shugoshin nevertheless helps to ensure the high fidelity of chromosome segregation at metaphase I. We propose that, in C. elegans, a LAB-1-mediated mechanism evolved to offset the challenges of providing protection against separase activity throughout a larger chromosome area.

Publication types

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

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Amino Acid Sequence
  • Animals
  • Aurora Kinase B
  • Aurora Kinases
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / antagonists & inhibitors
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Cycle Proteins / metabolism
  • Chromatids / genetics
  • Chromatids / metabolism
  • Chromosomal Proteins, Non-Histone / antagonists & inhibitors
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosome Segregation
  • DNA-Binding Proteins / metabolism
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / metabolism
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Developmental*
  • Immunoglobulin G / immunology
  • Meiosis / physiology
  • Meiotic Prophase I / physiology
  • Mitosis / physiology
  • Molecular Sequence Data
  • Multiprotein Complexes / metabolism
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • RNA, Helminth / genetics
  • RNA, Helminth / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Sister Chromatid Exchange

Substances

  • Caenorhabditis elegans Proteins
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Immunoglobulin G
  • LAB-1 protein, C elegans
  • Multiprotein Complexes
  • RNA, Helminth
  • RNA, Messenger
  • RNA, Small Interfering
  • cohesins
  • condensin complexes
  • Aurora Kinase B
  • Aurora Kinases
  • Protein Serine-Threonine Kinases
  • air-2 protein, C elegans
  • Adenosine Triphosphatases