Open AccessAmino Acid Transporter LAT3 Is Required for Podocyte Development and Function
Author(s) -
Yuji Sekine,
Yukino Nishibori,
Yoshihiro Akimoto,
Akihiko Kudo,
Noriko Ito,
Daisuke Fukuhara,
Ryota Kurayama,
Eiji Higashihara,
Ellappan Babu,
Yoshikatsu Kanai,
Katsuhiko Asanuma,
Masaaki Nagata,
Arunabha Majumdar,
Karl Tryggvason,
Yan Kou
Publication year - 2009
Publication title -
journal of the american society of nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.451
H-Index - 279
eISSN - 1533-3450
pISSN - 1046-6673
DOI - 10.1681/asn.2008070809
Subject(s) - podocyte , microbiology and biotechnology , glomerular basement membrane , zebrafish , immunoelectron microscopy , biology , kidney development , kidney , chemistry , endocrinology , biochemistry , glomerulonephritis , immunohistochemistry , immunology , gene , proteinuria , embryonic stem cell
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.