RRC ID 46295
著者 Chien SC, Brinkmann EM, Teuliere J, Garriga G.
タイトル Caenorhabditis elegans PIG-1/MELK acts in a conserved PAR-4/LKB1 polarity pathway to promote asymmetric neuroblast divisions.
ジャーナル Genetics
Abstract Asymmetric cell divisions produce daughter cells with distinct sizes and fates, a process important for generating cell diversity during development. Many Caenorhabditis elegans neuroblasts, including the posterior daughter of the Q cell (Q.p), divide to produce a larger neuron or neuronal precursor and a smaller cell that dies. These size and fate asymmetries require the gene pig-1, which encodes a protein orthologous to vertebrate MELK and belongs to the AMPK-related family of kinases. Members of this family can be phosphorylated and activated by the tumor suppressor kinase LKB1, a conserved polarity regulator of epithelial cells and neurons. In this study, we present evidence that the C. elegans orthologs of LKB1 (PAR-4) and its partners STRAD (STRD-1) and MO25 (MOP-25.2) regulate the asymmetry of the Q.p neuroblast division. We show that PAR-4 and STRD-1 act in the Q lineage and function genetically in the same pathway as PIG-1. A conserved threonine residue (T169) in the PIG-1 activation loop is essential for PIG-1 activity, consistent with the model that PAR-4 (or another PAR-4-regulated kinase) phosphorylates and activates PIG-1. We also demonstrate that PIG-1 localizes to centrosomes during cell divisions of the Q lineage, but this localization does not depend on T169 or PAR-4. We propose that a PAR-4-STRD-1 complex stimulates PIG-1 kinase activity to promote asymmetric neuroblast divisions and the generation of daughter cells with distinct fates. Changes in cell fate may underlie many of the abnormal behaviors exhibited by cells after loss of PAR-4 or LKB1.
巻・号 193(3)
ページ 897-909
公開日 2013-3-1
DOI 10.1534/genetics.112.148106
PII genetics.112.148106
PMID 23267054
PMC PMC3584005
MeSH Animals Asymmetric Cell Division / genetics* Caenorhabditis elegans / cytology Caenorhabditis elegans / enzymology* Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Carrier Proteins / genetics Carrier Proteins / metabolism Catalytic Domain Cell Lineage Centrosome / metabolism Neural Stem Cells / cytology* Neural Stem Cells / metabolism Phosphorylation Protein Serine-Threonine Kinases / chemistry Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism*
IF 4.015
引用数 19
WOS 分野 GENETICS & HEREDITY
リソース情報
線虫 tm3694