Kidney amino acid transport.
Near complete reabsorption of filtered amino acids is a main specialized transport function of the kidney proximal tubule. This evolutionary conserved task is carried out by a subset of luminal and basolateral transporters that together form the transcellular amino acid transport machinery similar to that of small intestine. A number of other amino acid transporters expressed in the basolateral membrane of proximal kidney tubule cells subserve either specialized metabolic functions, such as the production of ammonium, or are part of the cellular housekeeping equipment. A new finding is that the luminal Na(+)-dependent neutral amino acid transporters of the SLC6 family require an associated protein for their surface expression as shown for the Hartnup transporter B(0)AT1 (SLC6A19) and suggested for the L: -proline transporter SIT1 (IMINO(B), SLC6A20) and for B(0)AT3 (XT2, SLC6A18). This accessory subunit called collectrin (TMEM27) is homologous to the transmembrane anchor region of the renin-angiotensin system enzyme ACE2 that we have shown to function in small intestine as associated subunit of the luminal SLC6 transporters B(0)AT1 and SIT1. Some mutations of B(0)AT1 differentially interact with these accessory subunits, providing an explanation for differential intestinal phenotypes among Hartnup patients. The basolateral efflux of numerous amino acids from kidney tubular cells is mediated by heteromeric amino acid transporters that function as obligatory exchangers. Thus, other transporters within the same membrane need to mediate the net efflux of exchange substrates, controlling thereby the net basolateral amino transport and thus the intracellular amino acid concentration.
Verrey
François
F
Institute of Physiology, University of Zürich, Switzerland. verrey@access.uzh.ch
Singer
Dustin
D
Ramadan
Tamara
T
Vuille-dit-Bille
Raphael N
RN
Mariotta
Luca
L
Camargo
Simone M R
SM
D026905:Amino Acid Transport Systems / Q000378:metabolism*; D026921:Amino Acid Transport Systems, Neutral / Q000378:metabolism / Q000502:physiology; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D027321:Anion Transport Proteins / Q000502:physiology; D017920:Antiporters / Q000502:physiology; D001692:Biological Transport; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000502:physiology; D000076988:Sulfate Transporters
D026905:Amino Acid Transport Systems; D026921:Amino Acid Transport Systems, Neutral; D000596:Amino Acids; D027321:Anion Transport Proteins; D017920:Antiporters; C455627:SLC26A8 protein, human; C491436:SLC6A19 protein, human; D000076988:Sulfate Transporters