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
-
- Animals
- Cytoskeleton/metabolism
- Kidney Glomerulus/cytology
- Kidney Glomerulus/embryology
- Kidney Glomerulus/metabolism*
- Proto-Oncogene Proteins c-akt/metabolism
- Zebrafish
- Amino Acid Transport Systems, Basic/genetics
- Amino Acid Transport Systems, Basic/metabolism*
- Mice, Inbred ICR
- Cell Membrane/metabolism
- Podocytes/cytology
- Podocytes/metabolism*
- Actins/metabolism
- Male
- Glomerular Basement Membrane/metabolism
- Female
- Zebrafish Proteins/metabolism
- Mice
- Humans
- Glomerular Filtration Rate/physiology
- Cell Differentiation/physiology*
- Phosphorylation
- PubMed
- 19443642 Full text @ J. Am. Soc. Nephrol.
Citation
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. (2009) Amino Acid Transporter LAT3 Is Required for Podocyte Development and Function. Journal of the American Society of Nephrology : JASN. 20(7):1586-1596.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping