The retrograde signaling protein GUN1 regulates tetrapyrrole biosynthesis
- aGraduate School of Arts and Sciences, The University of Tokyo, Komaba, Meguro-ku, 153-8902 Tokyo, Japan;
- bSchool of Biological Sciences, University of Southampton, Southampton SO17 1BJ, United Kingdom;
- cGraduate School of Science, Kyoto University, Sakyo-ku, 606-8502 Kyoto, Japan;
- dDepartment of Bioscience, Tokyo University of Agriculture, Setagaya-ku, 156-8502 Tokyo, Japan;
- eLaboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama 226-8503, Japan;
- fSchool of Agriculture, Meiji University, Kawasaki-shi, 214-8571 Kanagawa, Japan;
- gPlant Molecular Biology, Faculty of Biology, Ludwig Maximilians Universität München, D-82152 Planegg-Martinsried, Germany;
- hInstitute for Life Sciences, University of Southampton, Southampton SO17 1BJ, United Kingdom
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Edited by Krishna K. Niyogi, University of California, Berkeley, CA, and approved October 22, 2019 (received for review July 2, 2019)

Significance
The signaling pathway between chloroplasts and the nucleus (retrograde signaling) is important for the correct development of the photosynthetic apparatus of plant seedlings. The pathway is still not understood, but the majority of mutants with altered signaling (gun mutants) implicate the tetrapyrrole molecule heme in this process. In this article, we have demonstrated that the major retrograde signaling protein GUN1 can bind tetrapyrroles and regulate the flow through the tetrapyrrole biosynthesis pathway. The results support a role for tetrapyrroles in mediating retrograde signaling and open up the opportunity to develop a unifying hypothesis for this pathway that takes account of all identified gun mutants.
Abstract
The biogenesis of the photosynthetic apparatus in developing seedlings requires the assembly of proteins encoded on both nuclear and chloroplast genomes. To coordinate this process there needs to be communication between these organelles, but the retrograde signals by which the chloroplast communicates with the nucleus at this time are still essentially unknown. The Arabidopsis thaliana genomes uncoupled (gun) mutants, that show elevated nuclear gene expression after chloroplast damage, have formed the basis of our understanding of retrograde signaling. Of the 6 reported gun mutations, 5 are in tetrapyrrole biosynthesis proteins and this has led to the development of a model for chloroplast-to-nucleus retrograde signaling in which ferrochelatase 1 (FC1)-dependent heme synthesis generates a positive signal promoting expression of photosynthesis-related genes. However, the molecular consequences of the strongest of the gun mutants, gun1, are poorly understood, preventing the development of a unifying hypothesis for chloroplast-to-nucleus signaling. Here, we show that GUN1 directly binds to heme and other porphyrins, reduces flux through the tetrapyrrole biosynthesis pathway to limit heme and protochlorophyllide synthesis, and can increase the chelatase activity of FC1. These results raise the possibility that the signaling role of GUN1 may be manifested through changes in tetrapyrrole metabolism, supporting a role for tetrapyrroles as mediators of a single biogenic chloroplast-to-nucleus retrograde signaling pathway.
Footnotes
↵1Present address: School of Life Sciences, University of Sussex, Brighton BN1 9QG, United Kingdom.
- ↵2To whom correspondence may be addressed. Email: ctmasuda{at}fye.c.u-tokyo.ac.jp.
Author contributions: M.J.T. and T.M. designed research; T. Shimizu, S.M.K., N.M., T. Shimada, K.T., Y.H., M.A., and T.M. performed research; T. Shimizu, S.M.K., A.N., S.W., T. Shimada, K.T., Y.H., M.A., D.L., H.O., M.J.T., and T.M. analyzed data; and N.M., M.J.T., and T.M. wrote the paper.
The authors declare no competing interest.
This article is a PNAS Direct Submission.
Data deposition: All plasmid constructs are available from Addgene (accession IDs 136357–136363).
This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.1911251116/-/DCSupplemental.
- Copyright © 2019 the Author(s). Published by PNAS.
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