An NAD+ biosynthetic pathway enzyme functions cell non-autonomously in C. elegans development

Matt Crook, Melanie R. Mcreynolds, Wenqing Wang, Wendy Hanna-Rose

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Background: Disruption of cellular metabolite levels can adversely impact development. Specifically, loss-of-function of the C. elegans NAD+ salvage biosynthesis gene PNC-1 results in an array of developmental phenotypes. Intriguingly, PNC-1 and its functional equivalent in vertebrates are secreted, but the contributions of the extracellular enzymes are poorly understood. We sought to study the tissue-specific requirements for PNC-1 expression and to examine the role of the secreted isoform. Results: A thorough analysis of PNC-1 expression did not detect expression in tissues that require PNC-1 function. Limited expression of both the secreted and intracellular PNC-1 isoforms provided function at a distance from the tissues with phenotypes. We also find that the secreted isoform contributes to in vivo PNC-1 activity. Furthermore, uv1 cell survival has the most stringent requirements in terms of PNC-1 expression pattern or level. Conclusions: Using careful promoter analysis and a restricted expression approach, we have shown that both the secreted and the intracellular PNC-1 isoforms function cell non-autonomously, and that the PNC-1a isoform is functionally relevant in vivo. Our work suggests a model where PNC-1 function is provided cell non-autonomously by a mix of intra and extracellular activity, most likely requiring NAD+ salvage metabolite transport between tissues. Developmental Dynamics 243:965-976, 2014.

Original languageEnglish (US)
Pages (from-to)965-976
Number of pages12
JournalDevelopmental Dynamics
Volume243
Issue number8
DOIs
StatePublished - Aug 2014

All Science Journal Classification (ASJC) codes

  • Developmental Biology

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