zyg-8, a gene required for spindle positioning in C. elegans, encodes a doublecortin-related kinase that promotes microtubule assembly

Dev Cell. 2001 Sep;1(3):363-75. doi: 10.1016/s1534-5807(01)00046-6.

Abstract

Proper spindle positioning is essential for spatial control of cell division. Here, we show that zyg-8 plays a key role in spindle positioning during asymmetric division of one-cell stage C. elegans embryos by promoting microtubule assembly during anaphase. ZYG-8 harbors a kinase domain and a domain related to Doublecortin, a microtubule-associated protein (MAP) affected in patients with neuronal migration disorders. Sequencing of zyg-8 mutant alleles demonstrates that both domains are essential for function. ZYG-8 binds to microtubules in vitro, colocalizes with microtubules in vivo, and promotes stabilization of microtubules to drug or cold depolymerization in COS-7 cells. Our findings demonstrate that ZYG-8 is a MAP crucial for proper spindle positioning in C. elegans, and indicate that the function of the Doublecortin domain in modulating microtubule dynamics is conserved across metazoan evolution.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Anaphase / physiology
  • Animals
  • COS Cells
  • Caenorhabditis elegans / drug effects
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinases / genetics
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cell Polarity
  • Female
  • Genes, Helminth
  • Genes, Reporter / genetics
  • Helminth Proteins / genetics*
  • Helminth Proteins / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Microscopy, Fluorescence
  • Microtubules / drug effects
  • Microtubules / metabolism*
  • Molecular Sequence Data
  • Nerve Tissue Proteins*
  • Nocodazole / pharmacology
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases*
  • Recombinant Fusion Proteins / metabolism
  • Sequence Alignment
  • Spindle Apparatus / drug effects
  • Spindle Apparatus / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • Helminth Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • Recombinant Fusion Proteins
  • zyg-8 protein, C elegans
  • DCLK1 protein, human
  • Protein-Serine-Threonine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Nocodazole