Role of dynamin, synaptojanin, and endophilin in podocyte foot processes

Keita Soda, Daniel M. Balkin, Shawn M. Ferguson, Summer Paradise, Ira Milosevic, Silvia Giovedi, Laura Volpicelli-Daley, Xuefei Tian, Yumei Wu, Hong Ma, Sung Hyun Son, Rena Zheng, Gilbert Moeckel, Ottavio Cremona, Lawrence B. Holzman, Pietro De Camilli, Shuta Ishibe

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)4401-4411
Number of pages11
JournalJournal of Clinical Investigation
Volume122
Issue number12
DOIs
Publication statusPublished - Dec 3 2012

Fingerprint

Dynamins
Podocytes
Glomerular Filtration Barrier
Maintenance
Endocytosis
Kidney
Synapses
Actins
Foot
Dynamin I
Clathrin
Synaptic Vesicles
Nephrotic Syndrome
Proteinuria
Embryonic Development
Proteins
synaptojanin
Neurons

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Soda, K., Balkin, D. M., Ferguson, S. M., Paradise, S., Milosevic, I., Giovedi, S., ... Ishibe, S. (2012). Role of dynamin, synaptojanin, and endophilin in podocyte foot processes. Journal of Clinical Investigation, 122(12), 4401-4411. https://doi.org/10.1172/JCI65289

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 journalArticle

Soda, K, Balkin, DM, Ferguson, SM, Paradise, S, Milosevic, I, Giovedi, S, Volpicelli-Daley, L, Tian, X, Wu, Y, Ma, H, Son, SH, Zheng, R, Moeckel, G, Cremona, O, Holzman, LB, De Camilli, P & Ishibe, S 2012, 'Role of dynamin, synaptojanin, and endophilin in podocyte foot processes', Journal of Clinical Investigation, vol. 122, no. 12, pp. 4401-4411. https://doi.org/10.1172/JCI65289
Soda K, Balkin DM, Ferguson SM, Paradise S, Milosevic I, Giovedi S et al. Role of dynamin, synaptojanin, and endophilin in podocyte foot processes. Journal of Clinical Investigation. 2012 Dec 3;122(12):4401-4411. https://doi.org/10.1172/JCI65289
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. / Role of dynamin, synaptojanin, and endophilin in podocyte foot processes. In: Journal of Clinical Investigation. 2012 ; Vol. 122, No. 12. pp. 4401-4411.
@article{ab99fb3c52d44ef49ad9aae38956aae0,
title = "Role of dynamin, synaptojanin, and endophilin in podocyte foot processes",
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.",
author = "Keita Soda and Balkin, {Daniel M.} and Ferguson, {Shawn M.} and Summer Paradise and Ira Milosevic and Silvia Giovedi and Laura Volpicelli-Daley and Xuefei Tian and Yumei Wu and Hong Ma and Son, {Sung Hyun} and Rena Zheng and Gilbert Moeckel and Ottavio Cremona and Holzman, {Lawrence B.} and {De Camilli}, Pietro and Shuta Ishibe",
year = "2012",
month = "12",
day = "3",
doi = "10.1172/JCI65289",
language = "English",
volume = "122",
pages = "4401--4411",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "12",

}

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 -