The podocyte slit diaphragm--from a thin grey line to a complex signalling hub
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The podocyte slit diaphragm--from a thin grey line to a complex signalling hub. / Grahammer, Florian; Schell, Christoph; Huber, Tobias B.
In: NAT REV NEPHROL, Vol. 9, No. 10, 10.2013, p. 587-98.Research output: SCORING: Contribution to journal › SCORING: Review article › Research
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TY - JOUR
T1 - The podocyte slit diaphragm--from a thin grey line to a complex signalling hub
AU - Grahammer, Florian
AU - Schell, Christoph
AU - Huber, Tobias B
PY - 2013/10
Y1 - 2013/10
N2 - The architectural design of our kidneys is amazingly complex, and culminates in the 3D structure of the glomerular filter. During filtration, plasma passes through a sieve consisting of a fenestrated endothelium and a broad basement membrane before it reaches the most unique part, the slit diaphragm, a specialized type of intercellular junction that connects neighbouring podocyte foot processes. When podocytes become stressed, irrespective of the causative stimulus, they undergo foot process effacement and loss of slit diaphragms--two key steps leading to proteinuria. Thus, proteinuria is the unifying denominator of a broad spectrum of podocytopathies. With the rising prevalence of chronic kidney disease and the fact that glomerular diseases account for the majority of patients with end-stage renal disease, further investigation and elucidation of this unique structure is of paramount importance. This Review recounts how perception of the slit diaphragm has changed over time as a result of intense research, from its first anatomical description as a thin intercellular connection, to an appreciation of its role as a dynamic signalling hub. These observations led to the introduction of novel concepts in podocyte biology, which could pave the way to development of highly desired, specific therapeutic strategies for glomerular diseases.
AB - The architectural design of our kidneys is amazingly complex, and culminates in the 3D structure of the glomerular filter. During filtration, plasma passes through a sieve consisting of a fenestrated endothelium and a broad basement membrane before it reaches the most unique part, the slit diaphragm, a specialized type of intercellular junction that connects neighbouring podocyte foot processes. When podocytes become stressed, irrespective of the causative stimulus, they undergo foot process effacement and loss of slit diaphragms--two key steps leading to proteinuria. Thus, proteinuria is the unifying denominator of a broad spectrum of podocytopathies. With the rising prevalence of chronic kidney disease and the fact that glomerular diseases account for the majority of patients with end-stage renal disease, further investigation and elucidation of this unique structure is of paramount importance. This Review recounts how perception of the slit diaphragm has changed over time as a result of intense research, from its first anatomical description as a thin intercellular connection, to an appreciation of its role as a dynamic signalling hub. These observations led to the introduction of novel concepts in podocyte biology, which could pave the way to development of highly desired, specific therapeutic strategies for glomerular diseases.
KW - Animals
KW - Glomerular Filtration Barrier
KW - Humans
KW - Intercellular Junctions
KW - Podocytes
KW - Renal Insufficiency, Chronic
KW - Signal Transduction
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
KW - Review
U2 - 10.1038/nrneph.2013.169
DO - 10.1038/nrneph.2013.169
M3 - SCORING: Review article
C2 - 23999399
VL - 9
SP - 587
EP - 598
JO - NAT REV NEPHROL
JF - NAT REV NEPHROL
SN - 1759-5061
IS - 10
ER -
