spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online October 9, 2009
doi: 10.1242/10.1242/dev.028431

Development 136, 3637-3646 (2009)
Published by The Company of Biologists 2009
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Related articles in Development
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Vrablik, T. L.
Right arrow Articles by Hanna-Rose, W.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vrablik, T. L.
Right arrow Articles by Hanna-Rose, W.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Nicotinamidase modulation of NAD+ biosynthesis and nicotinamide levels separately affect reproductive development and cell survival in C. elegans

Tracy L. Vrablik*, Li Huang*,{dagger}, Stephanie E. Lange and Wendy Hanna-Rose{ddagger}

Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA.

{ddagger} Author for correspondence (wxh21{at}psu.edu)

Accepted 1 September 2009

Nicotinamide adenine dinucleotide (NAD+) is a central molecule in cellular metabolism and an obligate co-substrate for NAD+-consuming enzymes, which regulate key biological processes such as longevity and stress responses. Although NAD+ biosynthesis has been intensely studied, little analysis has been done in developmental models. We have uncovered novel developmental roles for a nicotinamidase (PNC), the first enzyme in the NAD+ salvage pathway of invertebrates. Mutations in the Caenorhabditis elegans nicotinamidase PNC-1 cause developmental and functional defects in the reproductive system; the development of the gonad is delayed, four uterine cells die by necrosis and the mutant animals are egg-laying defective. The temporal delay in gonad development results from depletion of the salvage pathway product NAD+, whereas the uv1 cell necrosis and egg-laying defects result from accumulation of the substrate nicotinamide. Thus, regulation of both substrate and product level is key to the biological activity of PNC-1. We also find that diet probably affects the levels of these metabolites, as it affects phenotypes. Finally, we identified a secreted isoform of PNC-1 and confirmed its extracellular localization and functional activity in vivo. We demonstrate that nicotinamide phosphoribosyltransferase (Nampt), the equivalent enzyme in nicotinamide recycling to NAD+ in vertebrates, can functionally substitute for PNC-1. As Nampt is also secreted, we postulate an evolutionarily conserved extracellular role for NAD+ biosynthetic enzymes during development and physiology.

Key words: Pnc1, Npt1, Nicotinic acid, PBEF, Visfatin


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?

Related articles in Development:

NAD+ your average developmental signal

Development 2009 136: e2102. [Full Text]  





© The Company of Biologists Ltd 2009