# Defining the Retrograde Plastid-to-Nucleus Stress Signaling Pathway

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA RIVERSIDE · 2020 · $318,775

## Abstract

ABSTRACT
 Retrograde signaling is an essential organelles-to-nucleus communication pathway, central to maintenance
of cellular homoeostasis in response to developmental and environmental inputs. We have identified the first
stress-specific plastid-to-nucleus retrograde signaling metabolite, methylerythritol cyclodiphosphate (MEcPP),
an isoprenoid precursor produced by the non-mevalonate methylerythritol phosphate (MEP) pathway. This is a
conserved signaling pathway present in plants, pathogenic bacteria and the parasite, malaria, but absent in
animals. As such, it has provided a validated target for the development of antibacterial and antimalarial agents.
 The long-term goal of our research is to delineate the perception and signal transduction components of
MEcPP-mediated signaling cascade. This competitive renewal proposal specifically aims at delineating:
I. Cellular components of the MEcPP retrograde signaling pathway
 To identify the components responsible for the perception and transduction of the MEcPP signal, we will
initially characterize the mutated genes in the two classes of suppressor lines that, despite their equally
constitutively elevated MEcPP levels, are either almost fully or only partially incapable of inducing MEcPP
response genes.
 Systematic characterization of these perception/signaling network components will provide fundamental
information regarding the underlying molecular mechanisms that link a single retrograde signaling molecule,
MEcPP, to its targeted ensemble of genes.
II. Molecular link between MEcPP and unfolded protein response in the ER
 Combined global transcriptome and proteome profiling, together with molecular genetics and
pharmacological approaches, has enabled us to identify MEcPP as an inducer of the Unfolded Protein Response
(UPR) in the endoplasmic reticulum (ER). We will decipher the MEcPP mechanism of action in induction of the
UPR, and conversely delineate the role of the UPR in MEcPP-mediated responses.
 This finding ushers novel insight into uncharted territories of interorganellar signaling, and will provide a
deeper understanding of key role of UPR in controlling principal mechanisms supporting robustness.
III. Governing components of stromule formation
 Imaging analyses of plants expressing a construct containing three chimeric marker genes that label plastids
with CFP, ER with YFP, and the nucleus with mCherry, has established a direct correlation between enhanced
MEcPP levels and increased presence of induced dynamic chloroplast tubular extensions called "stromules”,
that extend from plastids to ER to nucleus. We will perform comparative proteomic analyses of genotypes with
varying numbers of stromules to identify cellular machineries responsible for their formation and to test the
potential role of stromules as communication conduits.

## Key facts

- **NIH application ID:** 9873967
- **Project number:** 5R01GM107311-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA RIVERSIDE
- **Principal Investigator:** KATAYOON DEHESH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $318,775
- **Award type:** 5
- **Project period:** 2013-09-05 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9873967

## Citation

> US National Institutes of Health, RePORTER application 9873967, Defining the Retrograde Plastid-to-Nucleus Stress Signaling Pathway (5R01GM107311-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9873967. Licensed CC0.

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