title: Nephrin expression in adult rodent central nervous system and its interaction with glutamate receptors.
abstract: Nephrin is an immunoglobulin-like adhesion molecule first discovered as a major component of the podocyte slit diaphragm, where its integrity is essential to the function of the glomerular filtration barrier. Outside the kidney, nephrin has been shown in other restricted locations, most notably in the central nervous system (CNS) of embryonic and newborn rodents. With the aim of better characterizing nephrin expression and its role in the CNS of adult rodents, we studied its expression pattern and possible binding partners in CNS tissues and cultured neuronal cells and compared these data to those obtained in control renal tissues and podocyte cell cultures. Our results show that, besides a number of locations already found in embryos and newborns, endogenous nephrin in adult rodent CNS extends to the pons and corpus callosum and is expressed by granule cells and Purkinje cells of the cerebellum, with a characteristic alternating expression pattern. In primary neuronal cells we find nephrin expression close to synaptic proteins and demonstrate that nephrin co-immunoprecipitates with Fyn kinase, glutamate receptors and the scaffolding molecule PSD95, an assembly that is reminiscent of those made by synaptic adhesion molecules. This role seems to be confirmed by our findings of impaired maturation and reduced glutamate exocytosis occurring in Neuro2A cells upon nephrin silencing. Of note, we disclose that the very same nephrin interactions occur in renal glomeruli and cultured podocytes, supporting our hypothesis that podocytes organize and use similar molecular intercellular signalling modules to those used by neuronal cells.
authors.affiliation: Renal Research Laboratory, Department of Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and Fondazione D'Amico per la Ricerca sulle Malattie Renali, Milan, Italy.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Silvia
authors.initials: S
authors.lastname: Armelloni
authors.forename: Masami
authors.initials: M
authors.lastname: Ikehata
authors.forename: Alessandro
authors.initials: A
authors.lastname: Corbelli
authors.forename: Marzia
authors.initials: M
authors.lastname: Pesaresi
authors.forename: Novella
authors.initials: N
authors.lastname: Calvaresi
authors.forename: Laura
authors.initials: L
authors.lastname: Giardino
authors.forename: Deborah
authors.initials: D
authors.lastname: Mattinzoli
authors.forename: Francesca
authors.initials: F
authors.lastname: Nisticò
authors.forename: Serena
authors.initials: S
authors.lastname: Andreoni
authors.forename: Aldamaria
authors.initials: A
authors.lastname: Puliti
authors.forename: Roberto
authors.initials: R
authors.lastname: Ravazzolo
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Forloni
authors.forename: Piergiorgio
authors.initials: P
authors.lastname: Messa
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Rastaldi
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins; D009474:Neurons / Q000378:metabolism; D050199:Podocytes / Q000378:metabolism; D011505:Protein-Tyrosine Kinases; D011689:Purkinje Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D017470:Receptors, Glutamate; C113267:nephrin; C490511:Frk protein, rat; D011505:Protein-Tyrosine Kinases; C490512:Frk protein, mouse; D019061:src-Family Kinases