Integrated Dual-Channel Retrograde Signaling Directs Stress Responses by Degrading the HAT1/TPL/IMPalpha-9 Suppressor Complex and Activating CAMTA3

Abstract

The intricate communication between plastids and the nucleus, shaping stress-responsive gene expression, has long intrigued researchers. This study combines genetics, biochemical analysis, cellular biology, and protein modeling to uncover how the plastidial metabolite MEcPP activates the stress-response regulatory hub known as the Rapid Stress Response Element (RSRE). Specifically, we identify the HAT1/TPL/IMP- 9 suppressor complex, where HAT1 directly binds to RSRE and its activator, CAMTA3, masking RSRE and sequestering the activator. Stress-induced MEcPP disrupts this complex, exposing RSRE and releasing CAMTA3, while enhancing Ca2+ influx and raising nuclear Ca2+levels crucial for CAMTA3 activation and the initiation of RSRE- containing gene transcription. This coordinated breakdown of the suppressor complex and activation of the activator highlights the dual-channel role of MEcPP in plastid-to- nucleus signaling. It further signifies how this metabolite transcends its expected biochemical role, emerging as a crucial initiator of harmonious signaling cascades essential for maintaining cellular homeostasis under stress. SummaryThis study uncovers how the stress-induced signaling metabolite MEcPP disrupts the HAT1/TPL/IMP-9 suppressor complex, liberating the activator CAMTA3 and enabling Ca2+ influx essential for CAMTA3 activation, thus orchestrating stress responses via repressor degradation and activator induction.