Regulation of the C. elegans molt by pqn-47

Abstract

C. elegans molts at the end of each of its four larval stages but this cycle ceases at the reproductive adult stage. We have identified a regulator of molting, pqn-47. Null mutations in pqn-47 cause a developmental arrest at the first larval molt, showing that this gene activity is required to transit the molt. Mutants with weak alleles of pqn-47 complete the larval molts but fail to exit the molting cycle at the adult stage. These phenotypes suggest that pqn-47 executes key aspects of the molting program including the cessation of molting cycles. The pqn-47 gene encodes a protein that is highly conserved in animal phylogeny but probably misannotated in genome sequences due to much less significant homology to a yeast transcription factor. A PQN-47∷GFP fusion gene is expressed in many neurons, vulval precursor cells, the distal tip cell (DTC), intestine, and the lateral hypodermal seam cells but not in the main body hypodermal syncytium (hyp7) that underlies, synthesizes, and releases most of the collagenous cuticle. A functional PQN-47∷GFP fusion protein localizes to the cytoplasm rather than the nucleus at all developmental stages, including the periods preceding and during ecdysis when genetic analysis suggests that pqn-47 functions. The cytoplasmic localization of PQN-47∷GFP partially overlaps with the endoplasmic reticulum, suggesting that PQN-47 is involved in the extensive secretion of cuticle components or hormones that occurs during molts. The mammalian and insect homologues of pqn-47 may serve similar roles in regulated secretion.

Myrf ER-Bound Transcription Factors Drive C. elegans Synaptic Plasticity via Cleavage-Dependent Nuclear Translocation

“…Next, using linkage analyses, we mapped ju1121 to myrf-1 (F59B10.1, previously named pqn-47 ) (Russel et al, 2011) and determined that ju1121 is a G-to-T change at nucleotide 821 of the myrf-1 open reading frame (Figure 1C). MYRF-1 is a C. elegans ortholog of the recently identified Myrf (myelin regulatory factor) family (Emery et al, 2009; Li and Richardson, 2016; Senoo et al, 2012).…”

“…A previous study reported that myrf-1 is widely expressed in many tissues, including neuronal, muscle, and epidermal seam cells (Russel et al, 2011). However, these initial analyses did not determine myrf-1 expression within specific neuronal subsets.…”

“…We then constructed a new transgene of the 4.7kb myrf-1 promoter and myrf-1 CDS that also includes the first two introns (Figure 3A). We inserted GFP in frame after Alanine 171 within a less conserved region, as described previously (Russel et al, 2011), and a Flag at the C-terminus immediately before the stop codon. Thus, GFP from this new transgene, referred as the myrf-1 minigene, could act as a reporter for both tissue expression patterns of myrf -1 and for MYRF-1 protein’s subcellular localization.…”

“…Myrf family genes are essential for organism development in mice (Emery et al, 2009), Dictyostelium (Senoo et al, 2012), and C. elegans (Russel et al, 2011). In mice, Myrf is specifically expressed in oligodendrocytes of the CNS (Emery et al, 2009) and critical for myelin development and maintenance (Emery et al, 2009; Koenning et al, 2012; Xiao et al, 2016).…”

MYRFs on the Move to Rewire Circuits

“…An earlier study in C. elegans found that Myrf-1 was predominantly endoplasmic reticulum (ER) localized (Russel et al, 2011). Intriguingly, mammalian studies showed that MYRF proteins undergo autocleavage in the ER membrane to separate a C-terminal transmembrane domain from an N-terminal DNA binding domain that translocates into the nucleus following cleavage (Bujalka et al, 2013;Li et al, 2013).…”