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, several similarities have been observed between mechanisms that govern podocyte organization and mechanisms 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. A role of dynamin in the maintenance of the kidney filtration barrier via an action on the actin cytoskeleton of podocytes was suggested. 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.
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Keita
authors.initials: K
authors.lastname: Soda
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Balkin
authors.forename: Shawn M
authors.initials: SM
authors.lastname: Ferguson
authors.forename: Summer
authors.initials: S
authors.lastname: Paradise
authors.forename: Ira
authors.initials: I
authors.lastname: Milosevic
authors.forename: Silvia
authors.initials: S
authors.lastname: Giovedi
authors.forename: Laura
authors.initials: L
authors.lastname: Volpicelli-Daley
authors.forename: Xuefei
authors.initials: X
authors.lastname: Tian
authors.forename: Yumei
authors.initials: Y
authors.lastname: Wu
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
authors.forename: Sung Hyun
authors.initials: SH
authors.lastname: Son
authors.forename: Rena
authors.initials: R
authors.lastname: Zheng
authors.forename: Gilbert
authors.initials: G
authors.lastname: Moeckel
authors.forename: Ottavio
authors.initials: O
authors.lastname: Cremona
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Holzman
authors.forename: Pietro
authors.initials: P
authors.lastname: De Camilli
authors.forename: Shuta
authors.initials: S
authors.lastname: Ishibe
mesh_terms: D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D034284:Dynamin I / Q000235:genetics* / Q000378:metabolism; D034285:Dynamin II / Q000235:genetics* / Q000378:metabolism; D004705:Endocytosis; D060730:Glomerular Filtration Barrier / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics* / Q000378:metabolism; D050199:Podocytes / Q000378:metabolism*; D011507:Proteinuria / Q000235:genetics / Q000473:pathology; D051437:Renal Insufficiency / Q000235:genetics / Q000473:pathology / Q000652:urine
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D009419:Nerve Tissue Proteins; C498434:Sh3gl2 protein, mouse; C097702:synaptojanin; D010744:Phosphoric Monoester Hydrolases; D034284:Dynamin I; D034285:Dynamin II