Research Paper Volume 9, Issue 5 pp 1414—1432
The protein kinase MBK-1 contributes to lifespan extension in daf-2 mutant and germline-deficient Caenorhabditis elegans
- 1 Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA
- 2 Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA
- 3 Present address: Institute for Biomedical Aging Research, Leopold-Franzens-Universität Innsbruck, Innsbruck, 6020, Austria
- 4 Present address: Calico Life Sciences, South San Francisco, CA 94080, USA
received: March 15, 2017 ; accepted: May 23, 2017 ; published: May 25, 2017 ;https://doi.org/10.18632/aging.101244
How to Cite
Copyright: Mack et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
In Caenorhabditis elegans, reduction of insulin/IGF-1 like signaling and loss of germline stem cells both increase lifespan by activating the conserved transcription factor DAF-16 (FOXO). While the mechanisms that regulate DAF-16 nuclear localization in response to insulin/IGF-1 like signaling are well characterized, the molecular pathways that act in parallel to regulate DAF-16 transcriptional activity, and the pathways that couple DAF-16 activity to germline status, are not fully understood at present. Here, we report that inactivation of MBK-1, the C. elegans ortholog of the human FOXO1-kinase DYRK1A substantially shortens the prolonged lifespan of daf-2 and glp-1 mutant animals while decreasing wild-type lifespan to a lesser extent. On the other hand, lifespan-reduction by mutation of the MBK-1-related kinase HPK-1 was not preferential for long-lived mutants. Interestingly, mbk-1 loss still allowed for DAF-16 nuclear accumulation but reduced expression of certain DAF-16 target genes in germline-less, but not in daf-2 mutant animals. These findings indicate that mbk-1 and daf-16 functionally interact in the germline- but not in the daf-2 pathway. Together, our data suggest mbk-1 as a novel regulator of C. elegans longevity upon both, germline ablation and DAF-2 inhibition, and provide evidence for mbk-1 regulating DAF-16 activity in germline-deficient animals.