PUBLICATION

Amino Acid Transporter LAT3 Is Required for Podocyte Development and Function

Authors
Sekine, Y., Nishibori, Y., Akimoto, Y., Kudo, A., Ito, N., Fukuhara, D., Kurayama, R., Higashihara, E., Babu, E., Kanai, Y., Asanuma, K., Nagata, M., Majumdar, A., Tryggvason, K., and Yan, K.
ID
ZDB-PUB-090518-25
Date
2009
Source
Journal of the American Society of Nephrology : JASN   20(7): 1586-1596 (Journal)
Registered Authors
Majumdar, Arindam
Keywords
none
MeSH Terms
  • Actins/metabolism
  • Amino Acid Transport Systems, Basic/genetics
  • Amino Acid Transport Systems, Basic/metabolism*
  • Animals
  • Cell Differentiation/physiology*
  • Cell Membrane/metabolism
  • Cytoskeleton/metabolism
  • Female
  • Glomerular Basement Membrane/metabolism
  • Glomerular Filtration Rate/physiology
  • Humans
  • Kidney Glomerulus/cytology
  • Kidney Glomerulus/embryology
  • Kidney Glomerulus/metabolism*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Phosphorylation
  • Podocytes/cytology
  • Podocytes/metabolism*
  • Proto-Oncogene Proteins c-akt/metabolism
  • Zebrafish
  • Zebrafish Proteins/metabolism
PubMed
19443642 Full text @ J. Am. Soc. Nephrol.
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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes