mTOR signalling in renal ion transport.
Anastasia AdellaJeroen H F de BaaijPublished in: Acta physiologica (Oxford, England) (2023)
The mammalian target of rapamycin (mTOR) signalling pathway is crucial in maintaining cell growth and metabolism. The mTOR protein kinase constitutes the catalytic subunit of two multimeric protein complexes called mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). As such, this pathway is indispensable for many organs, including the kidney. Since its discovery, mTOR has been associated with major renal disorders such as acute kidney injury, chronic kidney disease, and polycystic kidney disease. On top of that, emerging studies using pharmacological interventions and genetic disease models have unveiled mTOR role in renal tubular ion handling. Along the tubule, mTORC1 and mTORC2 subunits are ubiquitously expressed at mRNA level. Nevertheless, at the protein level, current studies suggest that a tubular segment-specific balance between mTORC1 and mTORC2 exist. In the proximal tubule, mTORC1 regulates nutrients transports through various transporters located in this segment. On the other hand, in the thick ascending limb of the loop of Henle, both complexes play a role in regulating NKCC2 expression and activity. Lastly, in the principal cells of the collecting duct, mTORC2 determines Na + reabsorption and K + excretion by regulating of SGK1 activation. Altogether, these studies establish the relevance of the mTOR signalling pathway in the pathophysiology of tubular solute transport. Despite extensive studies on the effectors of mTOR, the upstream activators of mTOR signalling remains elusive in most nephron segments. Further understanding of the role of growth factor signalling and nutrient sensing is essential to establish the exact role of mTOR in kidney physiology.
Keyphrases
- cell proliferation
- chronic kidney disease
- acute kidney injury
- binding protein
- oxidative stress
- gene expression
- dna methylation
- poor prognosis
- protein kinase
- coronary artery
- polycystic kidney disease
- end stage renal disease
- genome wide
- physical activity
- case control
- high glucose
- amino acid
- endothelial cells
- single cell
- cell death
- density functional theory