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Nephrocystin-1 interacts directly with Ack1 and is expressed in human collecting duct

Lookup NU author(s): Dr Lorraine Eley, Dr Shabbir Moochhala, Dr Roslyn Simms, Professor John Sayer

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Abstract

Nephronophthisis is characterised by renal fibrosis, tubular basement membrane disruption and corticomedullary cyst formation leading to end stage renal failure. Mutations in NPHP1 account for the underlying genetic defect in 25% of patients with nephronophthisis. Loss of urine concentration ability may be an early feature of nephronophthisis. Using yeast-2-library screening with the SH3 domain of nephrocystin-1 as bait, we identify Ack1 as a novel interaction partner. This interaction is confirmed using exogenous over-expression followed by co-immunoprecipitation. Ack1 is an activated Cdc42-associated kinase, and like nephrocystin-1, is a known interactor of p130Cas. Nephrocystin-1 partially colocalises with Ack1 at cell-cell contacts in IMCD3 cells. In human kidney, nephrocystin-1 expression is limited to cell-cell junctions in renal collecting duct cells. These data define Ack1 as a novel interaction partner of nephrocystin-1 and implicate cell-cell junctions and the renal collecting duct in the pathology of nephronophthisis. © 2008 Elsevier Inc. All rights reserved.


Publication metadata

Author(s): Eley L, Moochhala SH, Simms R, Hildebrandt F, Sayer JA

Publication type: Article

Publication status: Published

Journal: Biochemical and Biophysical Research Communications

Year: 2008

Volume: 371

Issue: 4

Pages: 877-882

ISSN (print): 0006-291X

ISSN (electronic): 1090-2104

Publisher: Academic Press

URL: http://dx.doi.org/10.1016/j.bbrc.2008.05.016

DOI: 10.1016/j.bbrc.2008.05.016

PubMed id: 18477472


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