A Sensor-to-Initiation Proteome Architecture Governing Regeneration Commitment in Turritopsis Species

Turritopsis species (Turritopsis
sp.) is well-known for its remarkable adaptability to environmental
stress and its capacity for rejuvenation The current study was undertaken
to identify an upstream cue that senses stress changes in the external
milieu and governs a binary fate decision to maintain dormancy or
unlock regeneration. We performed proteome-scale profiling across
the cyst and early stolon stages of Turritopsis sp.,
with an emphasis on extracellular signaling and translational control.
Proteome dynamics from the cyst to early stolon stage converge on
a coherent “sensor-to initiation” architecture, including
a sensor layer (TRP/PIEZO mechanotransducers, purinergic receptors,
and integrin/FAK), an initiation layer (mTORC1–eIF4F signaling),
and a stress-modulation layer (PERK–ISR signaling). We also
nominate three actionable upstream hubs whose changes could be sufficient,
in principle, to create a pro-translation state: CUL3–Kelch
adaptors, Rag GTPase regulators and FKBP8-linked quality-control nodes.
We therefore we propose a compact, testable mechanism for regeneration
commitment in which sensor-integrated cues drive a calibrated mTORC1–eIF4F
“initiation switch” buffered by a protective ISR. The
identification of CUL3–Kelch, Rag GTPases, and FKBP8 as leverage
points yields immediate hypotheses for transiently unlocking initiation
to hasten repair.