HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Summary Full Text Full Text (PDF) Supplemental Data All Versions of this Article: fj.05-4962fjev1 20/7/976    most recent Alert me when this article is cited Alert me if a correction is posted 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 Citing Articles via Google Scholar Google Scholar Articles by Rastaldi, M. P. Articles by D’Amico, G. Search for Related Content PubMed PubMed Citation Articles by Rastaldi, M. P. Articles by D’Amico, G.

Glomerular podocytes contain neuron-like functional synaptic vesicles

Maria Pia Rastaldi^*, Silvia Armelloni^*, Silvia Berra^*, Novella Calvaresi^*, Alessandro Corbelli^*, Laura Anna Giardino^*, Min Li^*, Guo Quin Wang^*, Alessandro Fornasieri^*, Antonello Villa, Eija Heikkila, Rabah Soliymani, Anissa Boucherot^||, Clemens David Cohen^||, Matthias Kretzler^||, Almut Nitsche^¶, Maddalena Ripamonti^#, Antonio Malgaroli^#, Marzia Pesaresi^*,**, Gian Luigi Forloni^**, Detlef Schlöndorff^||, Harry Holthofer and Giuseppe D’Amico^*

^* Renal Immunopathology Laboratory, Associazione Nuova Nefrologia, Fondazione D’Amico per la Ricerca sulle Malattie Renali, c/o Department of Nephrology and Immunology, San Carlo Hospital, Milan, Italy;

Microscopy and Image Analysis Consortium, Department of Neurosciences and Biomedical Technologies, Milano Bicocca University, Monza, Italy;

Molecular Medicine, Biomedicum Helsinki, Helsinki, Finland;

Protein Chemistry Unit, Biomedicum Helsinki, Helsinki, Finland;

^|| Medical Policlinic, University of Munich, Munich, Germany;

^¶ Sanofi-Aventis, Frankfurt, Germany;

^# Neurobiology of Learning Unit, Universita’ Vita-Salute S. Raffaele, Segrate, Italy; and

^** Biology of Neurodegenerative Diseases Laboratory, Mario Negri Institute, Milan, Italy

¹Correspondence: Renal Immunopathology Laboratory, Associazione Nuova Nefrologia and Fondazione D’Amico per la Ricerca sulle Malattie Renali, c/o San Carlo Borromeo Hospital, via Pio II, 3, Milan 20153, Italy. E-mail mp.rastaldi{at}fastwebnet.it

ABSTRACT

Although patients with chronic renal failure are increasing worldwide, many aspects of kidney biology remain to be elucidated. Recent research has uncovered several molecular properties of the glomerular filtration barrier, in which podocytes, highly differentiated, ramified cells that enwrap the glomerular basement membrane, have been reported to be mainly responsible for filter’s selectivity. We previously described that podocytes express Rab3A, a GTPase restricted to cell types that are capable of highly regulated exocytosis, such as neuronal cells. Here, we first demonstrate by a proteomic study that Rab3A in podocytes coimmmunoprecipitates with molecules once thought to be synapse specific. We then show that podocytes possess structures resembling synaptic vesicles, which contain glutamate, coexpress Rab3A and synaptotagmin 1, and undergo spontaneous and stimulated exocytosis and recycling, with glutamate release. Finally, from the results of a cDNA microarray study, we describe the presence of a series of neuron- and synapse-specific molecules in normal human glomeruli and confirm the glomerular protein expression of both metabotropic and ionotropic glutamate receptors. These data point toward a synaptic-like mechanism of communication among glomerular cells, which perfectly fits with the molecular composition of the glomerular filter and puts in perspective several previous observations, proposing a different working hypothesis for understanding glomerular signaling dynamics.— Rastaldi, M. P., Armelloni, S., Berra, S., Calvaresi, N., Corbelli, A., Giardino, L. A., Li, M., Wang, G. Q., Fornasieri, A., Villa, A., Heikkila, E., Soliymani, R., Boucherot, A., Cohen, C. D., Kretzler, M., Nitsche, A., Ripamonti, M., Malgaroli, A., Pesaresi, M., Forloni, G. L., Schlöndorff, D., Holthofer, H., D’Amico, G. Glomerular podocytes contain neuron-like functional synaptic vesicles.

This article has been cited by other articles:

				N. Guillen, M. A. Navarro, C. Arnal, E. Noone, J. M. Arbones-Mainar, S. Acin, J. C. Surra, P. Muniesa, H. M. Roche, and J. Osada Microarray analysis of hepatic gene expression identifies new genes involved in steatotic liver Physiol Genomics, May 13, 2009; 37(3): 187 - 198. [Abstract] [Full Text] [PDF]

				S. Sato, J. Xu, S. Okuyama, L. B. Martinez, S. M. Walsh, M. T. Jacobsen, R. J. Swan, J. D. Schlautman, P. Ciborowski, and T. Ikezu Spatial Learning Impairment, Enhanced CDK5/p35 Activity, and Downregulation of NMDA Receptor Expression in Transgenic Mice Expressing Tau-Tubulin Kinase 1 J. Neurosci., December 31, 2008; 28(53): 14511 - 14521. [Abstract] [Full Text] [PDF]

				M. A. Saleem, J. Zavadil, M. Bailly, K. McGee, I. R. Witherden, H. Pavenstadt, H. Hsu, J. Sanday, S. C. Satchell, R. Lennon, et al. The molecular and functional phenotype of glomerular podocytes reveals key features of contractile smooth muscle cells Am J Physiol Renal Physiol, October 1, 2008; 295(4): F959 - F970. [Abstract] [Full Text] [PDF]

				H. Holthofer Molecular architecture of the glomerular slit diaphragm: lessons learnt for a better understanding of disease pathogenesis Nephrol. Dial. Transplant., August 1, 2007; 22(8): 2124 - 2128. [Full Text] [PDF]

				K. Asanuma, K. N. Campbell, K. Kim, C. Faul, and P. Mundel Nuclear relocation of the nephrin and CD2AP-binding protein dendrin promotes apoptosis of podocytes PNAS, June 12, 2007; 104(24): 10134 - 10139. [Abstract] [Full Text] [PDF]

				E. Bertelli, M. Regoli, L. Fonzi, R. Occhini, S. Mannucci, L. Ermini, and P. Toti Nestin Expression in Adult and Developing Human Kidney J. Histochem. Cytochem., April 1, 2007; 55(4): 411 - 421. [Abstract] [Full Text] [PDF]