# Multiple regulators constrain the abundance of Caenorhabditis elegans DLK-1 in ciliated sensory neurons

## TL;DR

This study explores how the DLK-1 protein is regulated in ciliated sensory neurons of C. elegans, identifying new genetic factors involved in its abundance and function.

## Contribution

The paper reports novel genetic regulators of DLK-1 abundance in ciliated sensory neurons, including a role for HSP90 and ODR-1 in this regulation.

## Key findings

- Mutants with increased GFP::DLK-1 accumulation were identified, including those affecting intraflagellar transport and cilia assembly.
- A novel HSP90 mutation causes misaccumulation of DLK-1 and up-regulation of CEBP-1 in ciliated sensory neurons.
- The guanylate cyclase ODR-1 constrains DLK-1 abundance in AWC neurons and affects ciliary morphology.

## Abstract

The conserved MAP3K DLKs are widely known for their functions in synapse formation, axonal regeneration and degeneration, and neuronal survival, notably under traumatic injury and chronic disease conditions. In contrast, their roles in other neuronal compartments are much less explored. Through an unbiased forward genetic screening in C. elegans for altered patterns of GFP-tagged DLK-1 expressed from the endogenous locus, we have recently uncovered a mechanism by which the abundance of DLK-1 is tightly regulated by intraflagellar transport in ciliated sensory neurons. Here, we report additional mutants identified from the genetic screen. Most mutants exhibit increased accumulation of GFP::DLK-1 in sensory endings, and the levels of misaccumulated GFP::DLK-1 are exacerbated by loss of function in cebp-1, the b-Zip transcription factor acting downstream of DLK-1. We identify several new mutations in genes encoding proteins functioning in intraflagellar transport and cilia assembly, in components of BBSome, MAPK-15, and DYF-5 kinases. We report a novel mutation in the chaperone HSP90 that causes misaccumulation of GFP::DLK-1 and up-regulation of CEBP-1 selectively in ciliated sensory neurons. We also find that the guanylate cyclase ODR-1 constrains GFP::DLK-1 abundance throughout cilia and dendrites of AWC neurons. Moreover, in odr-1 mutants, AWC cilia display distorted morphology, which is ameliorated by loss of function in dlk-1 or cebp-1. These data expand the landscape of DLK-1 signaling in ciliated sensory neurons and underscore a high degree of cell- and neurite- specific regulation.