RGD Reference Report - Nephrin forms a complex with adherens junction proteins and CASK in podocytes and in Madin-Darby canine kidney cells expressing nephrin. - Rat Genome Database

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Nephrin forms a complex with adherens junction proteins and CASK in podocytes and in Madin-Darby canine kidney cells expressing nephrin.

Authors: Lehtonen, S  Lehtonen, E  Kudlicka, K  Holthofer, H  Farquhar, MG 
Citation: Lehtonen S, etal., Am J Pathol. 2004 Sep;165(3):923-36.
RGD ID: 1600864
Pubmed: PMID:15331416   (View Abstract at PubMed)
PMCID: PMC1618613   (View Article at PubMed Central)
DOI: DOI:10.1016/S0002-9440(10)63354-8   (Journal Full-text)

Mutations in the NPHS1 gene encoding nephrin lead to congenital nephrotic syndrome of the Finnish type. Nephrin is a key component of the glomerular slit diaphragms between epithelial foot processes, but its role in the pathogenesis of this disease is poorly understood. To further clarify the molecular mechanisms involved we investigated the interactions between nephrin and other components of the foot processes and filtration slits, especially adherens junction proteins, and searched for novel nephrin interacting proteins. Using co-immunoprecipitation and pull-down assays we show here that nephrin forms a multiprotein complex with cadherins and p120 catenin and with three scaffolding proteins, ZO-1, CD2AP, and CASK, in kidney glomeruli and when expressed in Madin-Darby canine kidney cells. CASK was identified as a novel binding partner of nephrin by mass spectrometry and was localized to podocytes in the glomerulus. CASK is a scaffolding protein that participates in maintenance of polarized epithelial cell architecture by linking membrane proteins and signaling molecules to the actin cytoskeleton. Our results support a model whereby the glomerular slit diaphragms are composed of cell adhesion molecules of the immunoglobulin and cadherin superfamilies that are connected to each other and to the actin cytoskeleton and signaling networks via the cytoplasmic scaffolding proteins CASK, CD2AP, and ZO-1.



Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Actn4Ratprotein-containing complex  IDA  RGD 
CaskRatprotein-containing complex  IDA  RGD 
Iqgap1Ratprotein-containing complex  IDA  RGD 
Magi2Ratprotein-containing complex  IDA  RGD 
Nphs1Ratprotein-containing complex  IDA  RGD 
Sptan1Ratprotein-containing complex  IDA  RGD 
Sptbn1Ratprotein-containing complex  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Actn4  (actinin alpha 4)
Cask  (calcium/calmodulin dependent serine protein kinase)
Iqgap1  (IQ motif containing GTPase activating protein 1)
Magi2  (membrane associated guanylate kinase, WW and PDZ domain containing 2)
Nphs1  (NPHS1 adhesion molecule, nephrin)
Sptan1  (spectrin, alpha, non-erythrocytic 1)
Sptbn1  (spectrin, beta, non-erythrocytic 1)


Additional Information