PMID- 10393930
OWN - NLM
STAT- MEDLINE
DCOM- 19990826
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 14
DP  - 1999 Jul 6
TI  - Nephrin is specifically located at the slit diaphragm of glomerular podocytes.
PG  - 7962-7
AB  - We describe here the size and location of nephrin, the first protein to be
      identified at the glomerular podocyte slit diaphragm. In Western blots, nephrin
      antibodies generated against the two terminal extracellular Ig domains of
      recombinant human nephrin recognized a 180-kDa protein in lysates of human
      glomeruli and a 150-kDa protein in transfected COS-7 cell lysates. In
      immunofluorescence, antibodies to this transmembrane protein revealed reactivity 
      in the glomerular basement membrane region, whereas the podocyte cell bodies
      remained negative. In immunogold-stained thin sections, nephrin label was found
      at the slit between podocyte foot processes. The congenital nephrotic syndrome of
      the Finnish type (NPHS1), a disease in which the nephrin gene is mutated, is
      characterized by massive proteinuria already in utero and lack of slit diaphragm 
      and foot processes. These features, together with the now demonstrated
      localization of nephrin to the slit diaphragm area, suggests an essential role
      for this protein in the normal glomerular filtration barrier. A zipper-like model
      for nephrin assembly in the slit diaphragm is discussed, based on the present and
      previous data.
FAU - Ruotsalainen, V
AU  - Ruotsalainen V
AD  - Biocenter and Department of Biochemistry, University of Oulu, 90570 Oulu,
      Finland.
FAU - Ljungberg, P
AU  - Ljungberg P
FAU - Wartiovaara, J
AU  - Wartiovaara J
FAU - Lenkkeri, U
AU  - Lenkkeri U
FAU - Kestila, M
AU  - Kestila M
FAU - Jalanko, H
AU  - Jalanko H
FAU - Holmberg, C
AU  - Holmberg C
FAU - Tryggvason, K
AU  - Tryggvason K
LA  - eng
SI  - GENBANK/AF035835
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Membrane Proteins)
RN  - 0 (Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (nephrin)
SB  - IM
MH  - Cell Membrane/physiology/ultrastructure
MH  - Cloning, Molecular
MH  - Epithelial Cells/*physiology/*ultrastructure
MH  - Finland
MH  - Glomerular Filtration Rate
MH  - Humans
MH  - Kidney Glomerulus/*physiology/*ultrastructure
MH  - Membrane Proteins
MH  - Microscopy, Immunoelectron
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Nephrotic Syndrome/genetics
MH  - Polymerase Chain Reaction
MH  - Proteins/*analysis/*genetics
MH  - Recombinant Proteins/analysis
PMC - PMC22170
EDAT- 1999/07/08 00:00
MHDA- 1999/07/08 00:01
CRDT- 1999/07/08 00:00
PHST- 1999/07/08 00:00 [pubmed]
PHST- 1999/07/08 00:01 [medline]
PHST- 1999/07/08 00:00 [entrez]
AID - 10.1073/pnas.96.14.7962 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):7962-7. doi: 10.1073/pnas.96.14.7962.