SV2B is essential for the integrity of the glomerular filtration barrier

被引:13
作者
Fukusumi, Yoshiyasu [1 ]
Wakamatsu, Ayako [1 ]
Takashima, Natsumi [1 ]
Hasegawa, Eriko [1 ]
Miyauchi, Naoko [1 ]
Tomita, Masayuki [1 ]
Kawachi, Hiroshi [1 ]
机构
[1] Niigata Univ, Grad Sch Med & Dent Sci, Inst Nephrol, Dept Cell Biol, Niigata 9518510, Japan
关键词
SLIT DIAPHRAGM; RAT MODEL; PROTEIN; NEPHRIN; EXPRESSION; PODOCYTES; SYNAPTOTAGMIN; TERMINUS; MOLECULE; PODOCIN;
D O I
10.1038/labinvest.2015.39
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The glomerular visceral epithelial cell (podocyte) is characterized as a specialized structure of the interdigitating foot processes, covering the outer side of the glomerular basement membrane (GBM). The neighboring foot processes are connected by a slit diaphragm, which is a key structure regulating the barrier function of the glomerular capillary wall to prevent proteinuria. We have previously reported that synaptic vesicle protein 2 B (SV2B) is expressed in the podocyte and that the expression is clearly decreased in nephrotic models. However, the precise function of SV2B in the podocyte is unclear. To investigate the role of SV2B in maintaining the podocyte function and to better understand the function of the neuron-like vesicle expressing SV2B in the podocyte, we analyzed them with SV2B knockout (KO) mice. An increase in the amount of proteinuria, effacement of the foot process of the podocyte, and alterations of the GBM were detected in SV2B KO mice. It was also found that the expression of CD2AP, nephrin, and NEPH1, the functional molecules of the slit diaphragm, and laminin, a critical component of the GBM, is clearly altered in SV2B KO mice. Synaptotagmin and neurexin, which have a role in the synaptic vesicle docking in neurons, are downregulated in the kidney cortex of SV2B KO mice. We have previously reported that neurexin interacts with CD2AP, and the present study shows that SV2B interacts with CD2AP. These findings suggest that the SV2B-neurexin complex is involved in the formation and maintenance of the slit diaphragm. In addition, SV2B is densely expressed close to the cell surface in the presumptive podocyte in the early stage of glomerulogenesis. These results suggest that SV2B has an essential role in the formation and maintenance of the glomerular capillary wall.
引用
收藏
页码:534 / 545
页数:12
相关论文
共 38 条
[1]   Proteinuria and Glomerular Damage in Rab3A Knockout Mice Chronically Fed a High-Glucose Diet [J].
Armelloni, Silvia ;
Calvaresi, Novella ;
Ikehata, Masami ;
Corbelli, Alessandro ;
Mattinzoli, Deborah ;
Giardino, Laura A. ;
Li, Min ;
Messa, Piergiorgio ;
Rastaldi, Maria P. .
NEPHRON EXPERIMENTAL NEPHROLOGY, 2012, 120 (02) :E69-E80
[2]   Vps34 Deficiency Reveals the Importance of Endocytosis for Podocyte Homeostasis [J].
Bechtel, Wibke ;
Helmstaedter, Martin ;
Balica, Jan ;
Hartleben, Bjoern ;
Kiefer, Betina ;
Hrnjic, Fatima ;
Schell, Christoph ;
Kretz, Oliver ;
Liu, Shuya ;
Geist, Felix ;
Kerjaschki, Dontscho ;
Walz, Gerd ;
Huber, Tobias B. .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2013, 24 (05) :727-743
[3]   Intravital imaging of podocyte calcium in glomerular injury and disease [J].
Burford, James L. ;
Villanueva, Kane ;
Lam, Lisa ;
Riquier-Brison, Anne ;
Hackl, Matthias J. ;
Pippin, Jeffrey ;
Shankland, Stuart J. ;
Peti-Peterdi, Janos .
JOURNAL OF CLINICAL INVESTIGATION, 2014, 124 (05) :2050-2058
[4]   Proteinuria and perinatal lethality in mice lacking NEPH1, a novel protein with homology to NEPHRIN [J].
Donoviel, DB ;
Freed, DD ;
Vogel, H ;
Potter, DG ;
Hawkins, E ;
Barrish, JP ;
Mathur, BN ;
Turner, CA ;
Geske, R ;
Montgomery, CA ;
Starbuck, M ;
Brandt, M ;
Gupta, A ;
Ramirez-Solis, R ;
Zambrowicz, BP ;
Powell, DR .
MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (14) :4829-4836
[5]   Role of the conserved WHXL motif in the C terminus of synaptotagmin in synaptic vesicle docking [J].
Fukuda, M ;
Moreira, JE ;
Liu, V ;
Sugimori, M ;
Mikoshiba, K ;
Llinás, RR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (26) :14715-14719
[6]   Podocyte Glutamatergic Signaling Contributes to the Function of the Glomerular Filtration Barrier [J].
Giardino, Laura ;
Armelloni, Silvia ;
Corbelli, Alessandro ;
Mattinzoli, Deborah ;
Zennaro, Cristina ;
Guerrot, Dominique ;
Tourrel, Fabien ;
Ikehata, Masami ;
Li, Min ;
Berra, Silvia ;
Carraro, Michele ;
Messa, Piergiorgio ;
Rastaldi, Maria P. .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2009, 20 (09) :1929-1940
[7]   Nephrin and CD2AP associate with phosphoinositide 3-OH kinase and stimulate AKT-dependent signaling [J].
Huber, TB ;
Hartleben, B ;
Kim, J ;
Schmidts, M ;
Schermer, B ;
Keil, A ;
Egger, L ;
Lecha, RL ;
Borner, C ;
Pavenstädt, H ;
Shaw, AS ;
Walz, G ;
Benzing, T .
MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (14) :4917-4928
[8]   The carboxyl terminus of Neph family members binds to the PDZ domain protein zonula occludens-1 [J].
Huber, TB ;
Schmidts, M ;
Gerke, P ;
Schermer, B ;
Zahn, A ;
Hartleben, B ;
Sellin, L ;
Walz, G ;
Benzing, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (15) :13417-13421
[9]   SV2A and SV2B function as redundant Ca2+ regulators in neurotransmitter release [J].
Janz, R ;
Goda, Y ;
Geppert, M ;
Missler, M ;
Südhof, TC .
NEURON, 1999, 24 (04) :1003-1016
[10]   Slit diaphragm-reactive nephritogenic MAb 5-1-6 alters expression of ZO-1 in rat podocytes [J].
Kawachi, H ;
Kurihara, H ;
Topham, PS ;
Brown, D ;
Shia, MA ;
Orikasa, M ;
Shimizu, F ;
Salant, DJ .
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 1997, 273 (06) :F984-F993