CD2AP mutations are associated with sporadic nephrotic syndrome and focal segmental glomerulosclerosis (FSGS)

Gigante, Maddalena; Pontrelli, Paola; Montemurno, Eustacchio; Roca, Leonarda; Aucella, Filippo; Penza, R; Caridi, Gianluca; Ranieri, Elena; Ghiggeri, Gian Marco; Gesualdo, Loreto

doi:10.1093/ndt/gfn712

Cited by 103 publications

(91 citation statements)

References 17 publications

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“…However, SH3-3 is unique in being linked to a disease-associated mutation; a polymorphism (K301M) in SH3-3 may play a role in hereditary focal segmental glomerulosclerosis (5). Lys-301 lies outside of the canonical binding groove and so would not be expected to interfere directly with peptide ligand docking, raising questions as to its exact role.…”

Section: Discussionmentioning

confidence: 99%

“…Homozygous CD2AP Ϫ/Ϫ mice develop progressive glomerular malfunction caused by the loss of podocyte foot process integrity and die of renal failure within 6 -7 weeks (3). Mutations identified in CD2AP (single nucleotide polymorphisms or deletions leading to protein sequence changes) result in abnormal kidney function and proteinuria with nephrotic syndrome caused by focal segmental glomerulosclerosis (4,5).…”

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confidence: 99%

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Differential Recognition Preferences of the Three Src Homology 3 (SH3) Domains from the Adaptor CD2-associated Protein (CD2AP) and Direct Association with Ras and Rab Interactor 3 (RIN3)

Rouka

Simister

Janning

et al. 2015

Journal of Biological Chemistry

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Background:The CD2AP adaptor facilitates cell signaling using its in-built interaction modules (SH3 domains). Results: RIN3 was characterized as a novel CD2AP SH3 binding protein by biophysical and biochemical methods. Conclusion: CD2AP has many potential interactors and is probably a cellular hub. Significance: We reveal how protein modules can interact with families of related recognition motifs rather than a single motif.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Differential Recognition Preferences of the Three Src Homology 3 (SH3) Domains from the Adaptor CD2-associated Protein (CD2AP) and Direct Association with Ras and Rab Interactor 3 (RIN3)

Rouka

Simister

Janning

et al. 2015

Journal of Biological Chemistry

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“…However, the incidence of CD2AP and TRCP6 in our database of 400 cases of INS is less than 2%. 36,37 The development of next-generation techniques for molecular analysis will enable a more comprehensive analysis of all genes potentially involved in INS and characterization of patient populations in whom new therapies may be successful. Our study has limitations.…”

Section: Discussionmentioning

confidence: 99%

Rituximab in Children with Resistant Idiopathic Nephrotic Syndrome

Magnasco

Ravani

Edefonti

et al. 2012

Journal of the American Society of Nephrology

148

112

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Idiopathic nephrotic syndrome resistant to standard treatments remains a therapeutic dilemma in pediatric nephrology. To test whether the anti-CD20 monoclonal antibody rituximab may benefit these patients, we conducted an open-label, randomized, controlled trial in 31 children with idiopathic nephrotic syndrome unresponsive to the combination of calcineurin inhibitors and prednisone. All children continued prednisone and calcineurin inhibitors at the doses prescribed before enrollment, and one treatment group received two doses of rituximab (375 mg/m 2 intravenously) as add-on therapy. The mean age was 8 years (range, 2-16 years). Rituximab did not reduce proteinuria at 3 months (change, 212% [95% confidence interval, 273% to 110%]; P=0.77 in analysis of covariance model adjusted for baseline proteinuria). Additional adjustment for previous remission and interaction terms (treatment by baseline proteinuria and treatment by previous remission) did not change the results. In conclusion, these data do not support the addition of rituximab to prednisone and calcineurin inhibitors in children with resistant idiopathic nephrotic syndrome.

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“…Recent genetic studies identified podocin, encoded by NPHS2, as a mutant gene that causes autosomal recessive steroid-resistant nephritic syndrome [3,29]. Likewise, CD2-associated protein (CD2AP) mutations are associated with sporadic nephrotic syndrome and focal and segmental glomerulosclerosis [11,32]. These genomic studies lead to the determination of a molecular topology for SD, required for maintaining the homeostasis of podocytespodocytes [21].…”

mentioning

confidence: 99%

Decreases in Podocin, CD2-Associated Protein (CD2AP) and Tensin2 May Be Involved in Albuminuria during Septic Acute Renal Failure

Kato

Mizuno-Horikawa

Mizuno

2011

The Journal of Veterinary Medical Science

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ABSTRACT. Podocytes have a peculiar structure constituting slit diaphragm (SD) and foot process (FP), and play essential roles in the glomerular filtration barrier. There is now ample evidence that SD-and FP-associated molecules, such as podocin and CD2-associated protein (CD2AP), are down-regulated during albuminuria of chronic kidney disease. However, it is still unclear whether these molecules are altered during acute renal failure (ARF) with albuminuria. Using lipopolysaccharide (LPS)-treated mice as a model of septic ARF, we provide evidence that the expression of SD-and FP-associated molecules becomes faint, along with albuminuria. In the LPS-treated mice, urinary albumin levels gradually increased, associated with the elevation of blood urea nitrogen levels, indicating the successful induction of albuminuria during septic ARF. In this pathological process, glomerular podocin expression became faint, especially at 36 hr post-LPS challenge (i.e., a peak of albuminuria). Likewise, LPS treatment led to a significant decrease in CD2AP, an anchorage between podocin and F-actin. With regard to this, tensin2 is a novel molecule that stabilizes F-actin extension. Interestingly, glomerular tensin2 expression levels were also decreased during the albuminuric phase, associated with losses of glomerular F-actin and synaptopodin under septic states. As a result, there were some lesions of podocytic FP effacement, as shown by electron microscopy. Based on these data, we emphasize the importance of concomitant decreases in podocin, CD2AP and tensin2 during septic ARF-associated proteinuria.

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CD2AP mutations are associated with sporadic nephrotic syndrome and focal segmental glomerulosclerosis (FSGS)

Abstract: Our findings suggest that CD2AP mutations modify the interaction with CD2 in lymphocytes and alter the composition of the renal slit diaphragm.

Cited by 103 publications

References 17 publications

Differential Recognition Preferences of the Three Src Homology 3 (SH3) Domains from the Adaptor CD2-associated Protein (CD2AP) and Direct Association with Ras and Rab Interactor 3 (RIN3)

Differential Recognition Preferences of the Three Src Homology 3 (SH3) Domains from the Adaptor CD2-associated Protein (CD2AP) and Direct Association with Ras and Rab Interactor 3 (RIN3)

Rituximab in Children with Resistant Idiopathic Nephrotic Syndrome

Decreases in Podocin, CD2-Associated Protein (CD2AP) and Tensin2 May Be Involved in Albuminuria during Septic Acute Renal Failure

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