title: Amino acid transporter LAT3 is required for podocyte development and function.
abstract: 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.
authors.affiliation: Kyorin University School of Medicine, Department of Pediatrics, Mitaka, Tokyo 181-8611, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sekine
authors.forename: Yukino
authors.initials: Y
authors.lastname: Nishibori
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Akimoto
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kudo
authors.forename: Noriko
authors.initials: N
authors.lastname: Ito
authors.forename: Daisuke
authors.initials: D
authors.lastname: Fukuhara
authors.forename: Ryota
authors.initials: R
authors.lastname: Kurayama
authors.forename: Eiji
authors.initials: E
authors.lastname: Higashihara
authors.forename: Ellappan
authors.initials: E
authors.lastname: Babu
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Kanai
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Asanuma
authors.forename: Michio
authors.initials: M
authors.lastname: Nagata
authors.forename: Arindam
authors.initials: A
authors.lastname: Majumdar
authors.forename: Karl
authors.initials: K
authors.lastname: Tryggvason
authors.forename: Kunimasa
authors.initials: K
authors.lastname: Yan
mesh_terms: 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
chemical_list: 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