UNASSIGNED: @entity2199 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 @entity1 NEK kinase family members @entity68697 and @entity64679 . 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 @entity1 @entity35267 , 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 @entity8993 / @entity17893 , 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, @entity8993 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 @entity1 NEKs including @entity68697 and @entity64679 . Our findings provide the first genetic and in vivo evidence for a role of NEK family members in endocytosis, which may be evolutionarily conserved.

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

@entity1 :: ('9606', 'Species') :: ['mammalian'] @entity64679 :: ('140609', 'Gene') :: ['NEK7'] @entity68697 :: ('10783', 'Gene') :: ['NEK6'] @entity2199 :: ('6239', 'Species') :: ['Caenorhabditis elegans'] @entity35267 :: ('284086', 'Gene') :: ['NEK8'] @entity8993 :: ('4035', 'Gene') :: ['LRP-1'] @entity17893 :: ('4036', 'Gene') :: ['megalin']
@entity2199 :: (6239,Species) :: ['C. elegans']
