zyg-8, a gene required for spindle positioning in C. elegans, encodes a doublecortin-related kinase that promotes microtubule assembly.
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.
Gönczy
P
P
Swiss Institute for Experimental Cancer Research, Lausanne. pierre.gonczy@isrec.unil.ch
Bellanger
J M
JM
Kirkham
M
M
Pozniakowski
A
A
Baumer
K
K
Phillips
J B
JB
Hyman
A A
AA
D000595:Amino Acid Sequence; D000705:Anaphase / Q000502:physiology; D000818:Animals; D019556:COS Cells; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000196:embryology / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D016764:Cell Polarity; D000089742:Doublecortin-Like Kinases; D005260:Female; D017238:Genes, Helminth; D017930:Genes, Reporter / Q000235:genetics; D015801:Helminth Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D015739:Nocodazole / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016415:Sequence Alignment; D008941:Spindle Apparatus / Q000187:drug effects / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; C439929:zyg-8 protein, C elegans; C117347:DCLK1 protein, human; D000089742:Doublecortin-Like Kinases; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D015739:Nocodazole