Glomerular podocytes contain neuron-like functional synaptic vesicles.
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.
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. mp.rastaldi@fastwebnet.it
Maria Pia
MP
Rastaldi
Silvia
S
Armelloni
Silvia
S
Berra
Novella
N
Calvaresi
Alessandro
A
Corbelli
Laura Anna
LA
Giardino
Min
M
Li
Guo Quin
GQ
Wang
Alessandro
A
Fornasieri
Antonello
A
Villa
Eija
E
Heikkila
Rabah
R
Soliymani
Anissa
A
Boucherot
Clemens David
CD
Cohen
Matthias
M
Kretzler
Almut
A
Nitsche
Maddalena
M
Ripamonti
Antonio
A
Malgaroli
Marzia
M
Pesaresi
Gian Luigi
GL
Forloni
Detlef
D
Schlöndorff
Harry
H
Holthofer
Giuseppe
G
D'Amico
D000818:Animals; D002478:Cells, Cultured; D004705:Endocytosis / Q000502:physiology; D005089:Exocytosis / Q000502:physiology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D051379:Mice; D050199:Podocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D013111:Spider Venoms / Q000494:pharmacology; D013572:Synaptic Vesicles / Q000378:metabolism*; D050863:Synaptotagmin I / Q000235:genetics / Q000378:metabolism; D020826:rab3A GTP-Binding Protein / Q000378:metabolism
D013111:Spider Venoms; D050863:Synaptotagmin I; C494311:Syt1 protein, mouse; D018698:Glutamic Acid; C020763:alpha-latrotoxin; D020826:rab3A GTP-Binding Protein