PMID- 36906912
OWN - NLM
STAT- MEDLINE
DCOM- 20230428
LR  - 20230523
IS  - 1748-1716 (Electronic)
IS  - 1748-1708 (Linking)
VI  - 238
IP  - 1
DP  - 2023 May
TI  - mTOR signaling in renal ion transport.
PG  - e13960
LID - 10.1111/apha.13960 [doi]
AB  - The mammalian target of rapamycin (mTOR) signaling 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 
      exists. 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 
      signaling pathway in the pathophysiology of tubular solute transport. Despite 
      extensive studies on the effectors of mTOR, the upstream activators of mTOR 
      signaling remain elusive in most nephron segments. Further understanding of the 
      role of growth factor signaling and nutrient sensing is essential to establish 
      the exact role of mTOR in kidney physiology.
CI  - (c) 2023 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on 
      behalf of Scandinavian Physiological Society.
FAU - Adella, Anastasia
AU  - Adella A
AUID- ORCID: 0000-0001-5712-6112
AD  - Department of Medical BioSciences, Radboud University Medical Center, Nijmegen, 
      The Netherlands.
FAU - de Baaij, Jeroen H F
AU  - de Baaij JHF
AUID- ORCID: 0000-0003-2372-8486
AD  - Department of Medical BioSciences, Radboud University Medical Center, Nijmegen, 
      The Netherlands.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20230413
PL  - England
TA  - Acta Physiol (Oxf)
JT  - Acta physiologica (Oxford, England)
JID - 101262545
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - W36ZG6FT64 (Sirolimus)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Humans
MH  - *Acute Kidney Injury/metabolism
MH  - Kidney/metabolism
MH  - Mechanistic Target of Rapamycin Complex 1/metabolism
MH  - Mechanistic Target of Rapamycin Complex 2/metabolism
MH  - Signal Transduction/physiology
MH  - Sirolimus/metabolism/pharmacology
MH  - *TOR Serine-Threonine Kinases/metabolism
MH  - Biological Transport
OTO - NOTNLM
OT  - electrolyte transport
OT  - kidney physiology
OT  - mammalian target of rapamycin
OT  - tubular disorder
EDAT- 2023/03/13 06:00
MHDA- 2023/04/26 06:42
CRDT- 2023/03/12 14:16
PHST- 2023/02/15 00:00 [revised]
PHST- 2023/01/06 00:00 [received]
PHST- 2023/03/07 00:00 [accepted]
PHST- 2023/04/26 06:42 [medline]
PHST- 2023/03/13 06:00 [pubmed]
PHST- 2023/03/12 14:16 [entrez]
AID - 10.1111/apha.13960 [doi]
PST - ppublish
SO  - Acta Physiol (Oxf). 2023 May;238(1):e13960. doi: 10.1111/apha.13960. Epub 2023 
      Apr 13.