title: Albuminuria and glomerular damage in mice lacking the metabotropic glutamate receptor 1.
abstract: The metabotropic glutamate (mGlu) receptor 1 (GRM1) has been shown to play an important role in neuronal cells by triggering, through calcium release from intracellular stores, various signaling pathways that finally modulate neuron excitability, synaptic plasticity, and mechanisms of feedback regulation of neurotransmitter release. Herein, we show that Grm1 is expressed in glomerular podocytes and that a glomerular phenotype is exhibited by Grm1(crv4) mice carrying a spontaneous recessive inactivating mutation of the gene. Homozygous Grm1(crv4/crv4) and, to a lesser extent, heterozygous mice show albuminuria, podocyte foot process effacement, and reduced levels of nephrin and other proteins known to contribute to the maintenance of podocyte cell structure. Overall, the present data extend the role of mGlu1 receptor to the glomerular filtration barrier. The regulatory action of mGlu1 receptor in dendritic spine morphology and in the control of glutamate release is well acknowledged in neuronal cells. Analogously, we speculate that mGlu1 receptor may regulate foot process morphology and intercellular signaling in the podocyte.
authors.affiliation: Molecular Genetics and Cytogenetics Unit, G. Gaslini Institute, Genova, Italy. apuliti@unige.it
authors.forename: Aldamaria
authors.initials: A
authors.lastname: Puliti
authors.forename: Pia Irene Anna
authors.initials: PI
authors.lastname: Rossi
authors.forename: Gianluca
authors.initials: G
authors.lastname: Caridi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Corbelli
authors.forename: Masami
authors.initials: M
authors.lastname: Ikehata
authors.forename: Silvia
authors.initials: S
authors.lastname: Armelloni
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Cristina
authors.initials: C
authors.lastname: Zennaro
authors.forename: Valerio
authors.initials: V
authors.lastname: Conti
authors.forename: Carlotta Maria
authors.initials: CM
authors.lastname: Vaccari
authors.forename: Michela
authors.initials: M
authors.lastname: Cassanello
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Calevo
authors.forename: Laura
authors.initials: L
authors.lastname: Emionite
authors.forename: Roberto
authors.initials: R
authors.lastname: Ravazzolo
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Rastaldi
mesh_terms: D000419:Albuminuria / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004317:Doxorubicin / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000150:complications / Q000378:metabolism / Q000473:pathology; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D051379:Mice; D010641:Phenotype; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018094:Receptors, Metabotropic Glutamate / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D004317:Doxorubicin