Essential role for collectrin in renal amino acid transport.
Angiotensin -converting enzyme 2 (ACE2) is a regulator of the renin angiotensin system involved in acute lung failure, cardiovascular functions and severe acute respiratory syndrome (SARS) infections in mammals. A gene encoding a homologue to ACE2, termed collectrin (Tmem27), has been identified in immediate proximity to the ace2 locus. The in vivo function of collectrin was unclear. Here we report that targeted disruption of collectrin in mice results in a severe defect in renal amino acid uptake owing to downregulation of apical amino acid transporters in the kidney. Collectrin associates with multiple apical transporters and defines a novel group of renal amino acid transporters. Expression of collectrin in Xenopus oocytes and Madin-Darby canine kidney (MDCK) cells enhances amino acid transport by the transporter B(0)AT1. These data identify collectrin as a key regulator of renal amino acid uptake.
Danilczyk
Ursula
U
IMBA, Institute for Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr-Gasse 3, A-1030, Vienna, Austria.
Sarao
Renu
R
Remy
Christine
C
Benabbas
Chahira
C
Stange
Gerti
G
Richter
Andreas
A
Arya
Sudha
S
Pospisilik
J Andrew
JA
Singer
Dustin
D
Camargo
Simone M R
SM
Makrides
Victoria
V
Ramadan
Tamara
T
Verrey
Francois
F
Wagner
Carsten A
CA
Penninger
Josef M
JM
D026905:Amino Acid Transport Systems / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D016764:Cell Polarity; D004285:Dogs; D015536:Down-Regulation; D005260:Female; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009865:Oocytes / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D014981:Xenopus
D026905:Amino Acid Transport Systems; D000596:Amino Acids; D008562:Membrane Glycoproteins; C504407:Tmem27 protein, mouse; D014443:Tyrosine