Altered expression of junctional adhesion molecule 4 in injured podocytes.
Recent investigations have revealed the importance of glomerular podocytes with its diaphragm as the major filtration barrier. Junctional adhesion molecule 4 (JAM4) has been identified as a protein that interacts with membrane-associated guanyl kinase inverted (MAGI)-1 and is reported to be expressed on podocytes. To elucidate the role of JAM4 on podocytes, we examined the expression of JAM4 and MAGI-1 in normal and two different proteinuric rat models: puromycin aminonucleoside (PAN) nephropathy and anti-nephrin antibody-induced (ANA) nephropathy, one model with and one without effacement of podocyte foot processes. JAM4 was detected by immunomicroscopy at the apical membrane of normal podocytes. JAM4 immunostaining was focally increased in the podocytes in PAN nephropathy but not in ANA nephropathy. In proteinuric podocytes, the expression of JAM4 was distinct from that of MAGI-1 or other slit diaphragm molecules such as nephrin and ZO-1. Close colocalization of JAM4 and ezrin was maintained in PAN nephropathy. By immunoelectron microscopy, the signals for JAM4 were detected at the free apical membrane of the podocytes with effaced foot processes. Studies with selective detergent extract revealed that the subcellular localization of JAM4 was altered in PAN nephropathy. Thus the altered expression of JAM4 appears to be associated with morphological changes in podocytes and can be a useful marker of injured podocytes. JAM4 may have a different role at the apical membrane besides the role as a junctional molecule and is likely associated with the unique structure of this epithelium.
Harita
Yutaka
Y
Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Niigata 951-8510, Japan.
Miyauchi
Naoko
N
Karasawa
Tamaki
T
Suzuki
Koichi
K
Han
Gi Dong
GD
Koike
Hiroko
H
Igarashi
Takashi
T
Shimizu
Fujio
F
Kawachi
Hiroshi
H
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002522:Chlorocebus aethiops; D005260:Female; D051528:Guanylate Kinases / Q000378:metabolism*; D007120:Immunochemistry; D007668:Kidney / Q000196:embryology / Q000201:enzymology / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009401:Nephrosis / Q000209:etiology / Q000473:pathology*; D050199:Podocytes / Q000378:metabolism / Q000473:pathology; D011507:Proteinuria / Q000209:etiology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017385:Sequence Homology
D015815:Cell Adhesion Molecules; C492399:Igsf5 protein, rat; D008565:Membrane Proteins; D051528:Guanylate Kinases; C508141:Magi1 protein, rat