Clinical impact of research on the podocyte slit diaphragm.
This Review summarizes recent research on the podocyte slit diaphragm. A growing number of molecules that function at the slit diaphragm have been identified in patients with inherited and sporadic nephrotic syndromes. Genetic deletion of nearly all of these molecules results in proteinuria and effacement of foot processes. Nephrin, Neph1 and podocin seem to form a multifunctional receptor complex at the slit diaphragm. Most of the other components of the slit diaphragm interact directly with this complex, in many cases coupling slit diaphragm components to the podocyte's actin cytoskeleton. These molecular findings are being applied to patients with glomerular disease. Over the next decade, these data might help to improve disease classification and prediction of which patients will respond to immunosuppressive treatment.
Johnstone
Duncan B
DB
Division of Nephrology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-0676, USA.
Holzman
Lawrence B
LB
D015870:Gene Expression; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007365:Intercellular Junctions / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D009404:Nephrotic Syndrome / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology* / Q000628:therapy; D050199:Podocytes / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D047908:Intracellular Signaling Peptides and Proteins; C431137:KIRREL1 protein, human; D008565:Membrane Proteins; C407223:NPHS2 protein; C113267:nephrin