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This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: ASN.2008121286v1 20/9/1929    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Giardino, L. Articles by Rastaldi, M. P. PubMed PubMed Citation Articles by Giardino, L. Articles by Rastaldi, M. P. Related Collections Related Article

Podocyte Glutamatergic Signaling Contributes to the Function of the Glomerular Filtration Barrier

Laura Giardino^*, Silvia Armelloni^*, Alessandro Corbelli^*,, Deborah Mattinzoli^*, Cristina Zennaro, Dominique Guerrot^,||, Fabien Tourrel^¶, Masami Ikehata^*, Min Li^*, Silvia Berra^*, Michele Carraro^**, Piergiorgio Messa^*, and Maria P. Rastaldi^*

*Renal Research Laboratory and
Department of Nephrology, Dialysis, and Renal Transplantation, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena and Fondazione D'Amico per la Ricerca sulle Malattie Renali, Milan,
MIA Consortium for Microscopy and Image Analysis, Monza,
Renal Child Foundation, G. Gaslini Children's Hospital, Genoa, and
**University Department of Clinical and Experimental Medicine and Clinical and Experimental Neurosciences, University of Trieste, Trieste, Italy; and
Nephrology Department and
^¶Department of Anaesthetics and Intensive Care, Rouen University Hospital, Rouen, and
^||INSERM UMR S 702, Paris, France

Correspondence: Dr. Maria P. Rastaldi, Renal Research Laboratory, Fondazione IRCCS Policlinico and Fondazione D'Amico, Via Pace, 9-20122, Milan, Italy. Phone: 00390255033879; Fax: 00390248110814; E-mail: mp.rastaldi{at}fastwebnet.it

Received for publication December 20, 2008. Accepted for publication April 24, 2009.

Podocytes possess the complete machinery for glutamatergic signaling, raising the possibility that neuron-like signaling contributes to glomerular function. To test this, we studied mice and cells lacking Rab3A, a small GTPase that regulates glutamate exocytosis. In addition, we blocked the glutamate ionotropic N-methyl-D-aspartate receptor (NMDAR) with specific antagonists. In mice, the absence of Rab3A and blockade of NMDAR both associated with an increased urinary albumin/creatinine ratio. In humans, NMDAR blockade, obtained by addition of ketamine to general anesthesia, also had an albuminuric effect. In vitro, Rab3A-null podocytes displayed a dysregulated release of glutamate with higher rates of spontaneous exocytosis, explained by a reduction in Rab3A effectors resulting in freedom of vesicles from the actin cytoskeleton. In addition, NMDAR antagonism led to profound cytoskeletal remodeling and redistribution of nephrin in cultured podocytes; the addition of the agonist NMDA reversed these changes. In summary, these results suggest that glutamatergic signaling driven by podocytes contributes to the integrity of the glomerular filtration barrier and that derangements in this signaling may lead to proteinuric renal diseases.

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Signaling at the Slit: Podocytes Chat by Synaptic Transmission

Thomas Weide and Tobias B. Huber
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				T. Weide and T. B. Huber Signaling at the Slit: Podocytes Chat by Synaptic Transmission J. Am. Soc. Nephrol., September 1, 2009; 20(9): 1862 - 1864. [Full Text] [PDF]

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673