C. elegans NIMA-related kinases NEKL-2 and NEKL-3 are required for the completion of molting

Dev Biol. 2015 Feb 15;398(2):255-66. doi: 10.1016/j.ydbio.2014.12.008. Epub 2014 Dec 16.


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.

Keywords: C. elegans; Endocytosis; Kinases; Molting; NEK; NEKL-2; NEKL-3; hyp7.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 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


  • Biomarkers
  • Caenorhabditis elegans Proteins
  • NEKL-3 protein, C elegans
  • Green Fluorescent Proteins
  • Protein Kinases
  • NEKL-2 protein, C elegans
  • NIMA-Related Kinases