Muscle type-specific responses to NAD+ salvage biosynthesis promote muscle function in Caenorhabditis elegans

Tracy L. Vrablik, Wenqing Wang, Awani Upadhyay, Wendy Hanna-Rose

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Salvage biosynthesis of nicotinamide adenine dinucleotide (NAD+) from nicotinamide (NAM) lowers NAM levels and replenishes the critical molecule NAD+ after it is hydrolyzed. This pathway is emerging as a regulator of multiple biological processes. Here we probe the contribution of the NAM-NAD+ salvage pathway to muscle development and function using Caenorhabditis elegans. C. elegans males with mutations in the nicotinamidase pnc-1, which catalyzes the first step of this NAD+ salvage pathway, cannot mate due to a spicule muscle defect. Multiple muscle types are impaired in the hermaphrodites, including body wall muscles, pharyngeal muscles and vulval muscles. An active NAD+ salvage pathway is required for optimal function of each muscle cell type. However, we found surprising muscle-cell-type specificity in terms of both the timing and relative sensitivity to perturbation of NAD+ production or NAM levels. Active NAD+ biosynthesis during development is critical for function of the male spicule protractor muscles during adulthood, but these muscles can surprisingly do without salvage biosynthesis in adulthood under the conditions examined. The body wall muscles require ongoing NAD+ salvage biosynthesis both during development and adulthood for maximum function. The vulval muscles do not function in the presence of elevated NAM concentrations, but NAM supplementation is only slightly deleterious to body wall muscles during development or upon acute application in adults. Thus, the pathway plays distinct roles in different tissues. As NAM-NAD+ biosynthesis also impacts muscle differentiation in vertebrates, we propose that similar complexities may be found among vertebrate muscle cell types.

Original languageEnglish (US)
Pages (from-to)387-394
Number of pages8
JournalDevelopmental biology
Volume349
Issue number2
DOIs
StatePublished - Jan 15 2011

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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