Study reveals cellular and molecular mechanisms of hypoxic stress and inflammation

Ion channels, transports, and classic membrane receptors are immediately delivered to defined cellular membranes once they are synthesized in the cytoplasm.

Pore-forming proteins, or PFPs for short, are discharged as water-soluble proteins; when these non-classic membrane proteins reach their target cell membrane, they can modify their conformation expansively and transform into a transmembrane pore structure.

In earlier research works, scientists from the Kunming Institute of Zoology of the Chinese Academy of Sciences demonstrated a novel cell regulation method along with a molecular route on the basis of a new pore-forming protein and trefoil factor complex, or CAT, from Bombina maxima.

The team discovered that the secretory pore-forming protein forms a certain material channel by acting on the endolysosomes, and subsequently controls the functions and state of the cells.

Now, investigators from the Kunming Institute of Zoology and the University of Science and Technology of China have further demonstrated the oxygen-dependent homologous protein regulation mechanism of the secretory cell endolysosome channel. The study results were published online in the Journal of Biological Chemistry.

Called BmALP3, the paralog of CAT was initially detected. The BmALP3, albeit lacking the membrane pore-forming capacity, can potentially perceive environmental oxygen tension and be converted between homodimer and monomer. It would then negatively control the biological activity and assembly of CAT through disulfide-bond exchange.

When BmALP3 was deactivated under hypoxic conditions, it resulted in the discharge of the inhibitory state of the effector protein machine CAT and supported cell emergency and inflammatory reaction.

Fascinatingly, the structural foundation of oxygen-dependent regulation mode was suitably preserved in various plants and animals.

The study additionally consolidates the physiological function and biological importance of the secretory cell endolysosome channel pathway, and also offers new clues and concepts for detailed analysis of the molecular and cellular methods and mechanisms of inflammation and hypoxic stress.

Journal reference:

Wang, Q., et al. (2020) A cellular endolysosome-modulating pore-forming protein from a toad is negatively regulated by its paralog under oxidizing conditions.


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