RRC ID 45896
著者 Yochem J, Lažetić V, Bell L, Chen L, Fay D.
タイトル C. elegans NIMA-related kinases NEKL-2 and NEKL-3 are required for the completion of molting.
ジャーナル Dev Biol
Abstract Caenorhabditis elegans molting is a process during which the apical extracellular matrix of the epidermis, the cuticle, is remodeled through a process of degradation and re-synthesis. Using a genetic approach, we identified nekl-3 as essential for the completion of molting. NEKL-3 is highly similar to the mammalian NEK kinase family members NEK6 and NEK7. Animals homozygous for a hypomorphic mutation in nekl-3, sv3, had a novel molting defect in which the central body region, but not the head or tail, was unable to shed the old cuticle. In contrast, a null mutation in nekl-3, gk506, led to complete enclosure within the old cuticle. nekl-2, which is most similar to mammalian NEK8, was also essential for molting. Mosaic analyses demonstrated that NEKL-2 and NEKL-3 were specifically required within the large epidermal syncytium, hyp7, to facilitate molting. Consistent with this, NEKL-2 and NEKL-3 were expressed at the apical surface of hyp7 where they localized to small spheres or tubular structures. Inhibition of nekl-2, but not nekl-3, led to the mislocalization of LRP-1/megalin, a cell surface receptor for low-density lipoprotein (LDL)-binding proteins. In addition, nekl-2 inhibition led to the mislocalization of several other endosome-associated proteins. Notably, LRP-1 acts within hyp7 to facilitate completion of molting, suggesting at least one mechanism by which NEKL-2 may influence molting. Notably, our studies failed to reveal a requirement for NEKL-2 or NEKL-3 in cell division, a function reported for several mammalian NEKs including NEK6 and NEK7. Our findings provide the first genetic and in vivo evidence for a role of NEK family members in endocytosis, which may be evolutionarily conserved.
巻・号 398(2)
ページ 255-66
公開日 2015-2-15
DOI 10.1016/j.ydbio.2014.12.008
PII S0012-1606(14)00634-4
PMID 25523392
PMC PMC4314388
MeSH Alleles Amino Acid Sequence Animals Biomarkers / metabolism Caenorhabditis elegans / enzymology* Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Polarity Endocytosis Endosomes / metabolism Fluorescence Genes, Helminth Genes, Reporter Green Fluorescent Proteins / metabolism Molecular Sequence Data Molting* Mosaicism Mutation / genetics NIMA-Related Kinases Phenotype Phylogeny Protein Kinases / chemistry Protein Kinases / genetics Protein Kinases / metabolism* Sequence Alignment Subcutaneous Tissue / embryology Subcutaneous Tissue / metabolism
IF 2.896
引用数 7
WOS 分野 DEVELOPMENTAL BIOLOGY
リソース情報
線虫 tm290