Amino acid transporter LAT3 is required for podocyte development and function.
LAT3 is a Na+-independent neutral l-amino acid transporter recently isolated from a human hepatocellular carcinoma cell line. Although liver, skeletal muscle, and pancreas are known to express LAT3, the tissue distribution and physiologic function of this transporter are not completely understood. Here, we observed that glomeruli express LAT3. Immunofluorescence, confocal microscopy, and immunoelectron microscopy revealed that LAT3 localizes to the apical plasma membrane of podocyte foot processes. In mice, starvation upregulated glomerular LAT3, phosphorylated AKT1, reconstituted the actin network, and elongated foot processes. In the fetal kidney, we observed intense LAT3 expression at the capillary loops stage of renal development. Finally, zebrafish morphants lacking lat3 function showed collapsed glomeruli with thickened glomerular basement membranes. Permeability studies of the glomerular filtration barrier in these zebrafish morphants demonstrated a disruption of selective glomerular permeability. Our data suggest that LAT3 may play a crucial role in the development and maintenance of podocyte structure and function by regulating protein synthesis and the actin cytoskeleton.
Sekine
Yuji
Y
Kyorin University School of Medicine, Department of Pediatrics, Mitaka, Tokyo 181-8611, Japan.
Nishibori
Yukino
Y
Akimoto
Yoshihiro
Y
Kudo
Akihiko
A
Ito
Noriko
N
Fukuhara
Daisuke
D
Kurayama
Ryota
R
Higashihara
Eiji
E
Babu
Ellappan
E
Kanai
Yoshikatsu
Y
Asanuma
Katsuhiko
K
Nagata
Michio
M
Majumdar
Arindam
A
Tryggvason
Karl
K
Yan
Kunimasa
K
D000199:Actins / Q000378:metabolism; D026923:Amino Acid Transport Systems, Basic / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D005260:Female; D050533:Glomerular Basement Membrane / Q000378:metabolism; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007678:Kidney Glomerulus / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010766:Phosphorylation; D050199:Podocytes / Q000166:cytology / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism
D000199:Actins; D026923:Amino Acid Transport Systems, Basic; C542311:LAT3 protein, mouse; C469951:SLC7A6 protein, human; D029961:Zebrafish Proteins; D051057:Proto-Oncogene Proteins c-akt