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.
- URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11702948
Keywords: Amino Acid Sequence ; Anaphase/physiology ; Animals ; COS Cells ; Ca(2+)-Calmodulin Dependent Protein Kinase/genetics/*metabolism ; Caenorhabditis elegans/drug effects/embryology/*genetics ; Caenorhabditis elegans Proteins/chemistry/*genetics/metabolism ; Cell Polarity ; Female ; Genes ; Helminth ; Genes ; Reporter/genetics ; Helminth Proteins/*genetics/metabolism ; Humans ; Male ; Microscopy ; Fluorescence ; Microtubules/drug effects/*metabolism ; Mitotic Spindle Apparatus/drug effects/*metabolism ; Molecular Sequence Data ; *Nerve Tissue Proteins ; Nocodazole/pharmacology ; Protein Structure ; Tertiary ; *Protein-Serine-Threonine Kinases ; Recombinant Fusion Proteins/metabolism ; Research Support ; Non-U.S. Gov't ; Research Support ; U.S. Gov't ; P.H.S. ; Sequence Alignment
Swiss Institute for Experimental Cancer Research, Lausanne. pierre.Gönczy@isrec.unil.ch
Record created on 2006-08-24, modified on 2016-08-08