Abstract
Podocytes are specialized cells that play an integral role in the renal glomerular filtration barrier via their foot processes. The foot processes form a highly organized structure, the disruption of which causes nephrotic syndrome. Interestingly, the protein networks that govern podocyte organization are strikingly similar to the processes that mediate neuronal synapse development. Dynamin, synaptojanin, and endophilin are functional partners in synaptic vesicle recycling via interconnected actions in clathrin-mediated endocytosis and actin dynamics in neurons. Dynamin has previously been shown to play a role in the maintenance of the kidney glomerular filtration barrier. Here we used a conditional double-KO of dynamin 1 (Dnm1) and Dnm2 in mouse podocytes to confirm dynamin's role in podocyte foot process maintenance. In addition, we demonstrated that while synaptojanin 1 (Synj1) KO mice and endophilin 1 (Sh3gl2), endophilin 2 (Sh3gl1), and endophilin 3 (Sh3gl3) triple-KO mice had grossly normal embryonic development, these mutants failed to establish a normal filtration barrier and exhibited severe proteinuria due to abnormal podocyte foot process formation. These results strongly implicate a protein network that functions at the interface between endocytosis and actin at neuronal synapses in the formation and maintenance of the kidney glomerular filtration barrier.
| Original language | English |
|---|---|
| Pages (from-to) | 4401-4411 |
| Number of pages | 11 |
| Journal | Journal of Clinical Investigation |
| Volume | 122 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 3 2012 |
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ASJC Scopus subject areas
- Medicine(all)
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Role of dynamin, synaptojanin, and endophilin in podocyte foot processes. / Soda, Keita; Balkin, Daniel M.; Ferguson, Shawn M.; Paradise, Summer; Milosevic, Ira; Giovedi, Silvia; Volpicelli-Daley, Laura; Tian, Xuefei; Wu, Yumei; Ma, Hong; Son, Sung Hyun; Zheng, Rena; Moeckel, Gilbert; Cremona, Ottavio; Holzman, Lawrence B.; De Camilli, Pietro; Ishibe, Shuta.
In: Journal of Clinical Investigation, Vol. 122, No. 12, 03.12.2012, p. 4401-4411.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Role of dynamin, synaptojanin, and endophilin in podocyte foot processes
AU - Soda, Keita
AU - Balkin, Daniel M.
AU - Ferguson, Shawn M.
AU - Paradise, Summer
AU - Milosevic, Ira
AU - Giovedi, Silvia
AU - Volpicelli-Daley, Laura
AU - Tian, Xuefei
AU - Wu, Yumei
AU - Ma, Hong
AU - Son, Sung Hyun
AU - Zheng, Rena
AU - Moeckel, Gilbert
AU - Cremona, Ottavio
AU - Holzman, Lawrence B.
AU - De Camilli, Pietro
AU - Ishibe, Shuta
PY - 2012/12/3
Y1 - 2012/12/3
N2 - Podocytes are specialized cells that play an integral role in the renal glomerular filtration barrier via their foot processes. The foot processes form a highly organized structure, the disruption of which causes nephrotic syndrome. Interestingly, the protein networks that govern podocyte organization are strikingly similar to the processes that mediate neuronal synapse development. Dynamin, synaptojanin, and endophilin are functional partners in synaptic vesicle recycling via interconnected actions in clathrin-mediated endocytosis and actin dynamics in neurons. Dynamin has previously been shown to play a role in the maintenance of the kidney glomerular filtration barrier. Here we used a conditional double-KO of dynamin 1 (Dnm1) and Dnm2 in mouse podocytes to confirm dynamin's role in podocyte foot process maintenance. In addition, we demonstrated that while synaptojanin 1 (Synj1) KO mice and endophilin 1 (Sh3gl2), endophilin 2 (Sh3gl1), and endophilin 3 (Sh3gl3) triple-KO mice had grossly normal embryonic development, these mutants failed to establish a normal filtration barrier and exhibited severe proteinuria due to abnormal podocyte foot process formation. These results strongly implicate a protein network that functions at the interface between endocytosis and actin at neuronal synapses in the formation and maintenance of the kidney glomerular filtration barrier.
AB - Podocytes are specialized cells that play an integral role in the renal glomerular filtration barrier via their foot processes. The foot processes form a highly organized structure, the disruption of which causes nephrotic syndrome. Interestingly, the protein networks that govern podocyte organization are strikingly similar to the processes that mediate neuronal synapse development. Dynamin, synaptojanin, and endophilin are functional partners in synaptic vesicle recycling via interconnected actions in clathrin-mediated endocytosis and actin dynamics in neurons. Dynamin has previously been shown to play a role in the maintenance of the kidney glomerular filtration barrier. Here we used a conditional double-KO of dynamin 1 (Dnm1) and Dnm2 in mouse podocytes to confirm dynamin's role in podocyte foot process maintenance. In addition, we demonstrated that while synaptojanin 1 (Synj1) KO mice and endophilin 1 (Sh3gl2), endophilin 2 (Sh3gl1), and endophilin 3 (Sh3gl3) triple-KO mice had grossly normal embryonic development, these mutants failed to establish a normal filtration barrier and exhibited severe proteinuria due to abnormal podocyte foot process formation. These results strongly implicate a protein network that functions at the interface between endocytosis and actin at neuronal synapses in the formation and maintenance of the kidney glomerular filtration barrier.
UR - http://www.scopus.com/inward/record.url?scp=84870523768&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84870523768&partnerID=8YFLogxK
U2 - 10.1172/JCI65289
DO - 10.1172/JCI65289
M3 - Article
C2 - 23187129
AN - SCOPUS:84870523768
VL - 122
SP - 4401
EP - 4411
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 12
ER -