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- Title
Ligation of α-Dystroglycan on Podocytes Induces Intracellular Signaling: A New Mechanism for Podocyte Effacement?
- Authors
Vogtländer, Nils P. J.; Visch, Henk Jan; Bakker, Marinka A. H.; Berden, Jo H. M.; van der Vlag, Johan
- Abstract
Background: α-Dystroglycan is a negatively charged glycoprotein that covers the apical and basolateral membrane of the podocyte. Its transmembrane binding to the cytoskeleton is regulated via tyrosine phosphorylation (pY892) of bdystroglycan. At the basolateral side α-dystroglycan binds the glomerular basement membrane. At the apical membrane, it plays a role in the maintenance of the filtration slit. In this study, we evaluated whether ligation of α-dystroglycan with specific antibodies or natural ligands induces intracellular signaling, and whether there is an effect on podocyte architecture. Methodology/Principal Findings: Conditionally immortalized podocytes were exposed in vitro to antibodies to adystroglycan, and to fibronectin, biglycan, laminin and agrin. Intracellular calcium fluxes, phosphorylation of β-dystroglycan and podocyte architecture were studied. Antibodies to α-dystroglycan could specifically induce calcium signaling. Fibronectin also induced calcium signaling, and led to dephosphorylation of pY892 in β-dystroglycan. Ligation of adystroglycan resulted in an altered actin architecture, a decreased number of podocyte pedicles and a more flattened appearance of the podocyte. Conclusions/Significance: We conclude that ligation of α-dystroglycan on podocytes induces intracellular calcium signaling, which leads to an altered cytoskeleton architecture akin to the situation of foot process effacement. In particular the ability of fibronectin to induce intracellular signaling events is of interest, since the expression and excretion of this protein is upregulated in several proteinuric diseases. Therefore, fibronectin-induced signaling via dystroglycan may be a novel mechanism for foot process effacement in proteinuric diseases.
- Subjects
GLYCOPROTEINS; CYTOSKELETON; MEMBRANE distillation; TYROSINE; IMMUNOGLOBULINS; FIBRONECTINS
- Publication
PLoS ONE, 2009, Vol 4, Issue 6, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0005979