Defects in ciliary localization of Nek8 is associated with cystogenesis

Pediatric Nephrology : Journal of the International Pediatric Nephrology Association
Melissa L TrappLynne M Quarmby

Abstract

Mutations in the human NIMA (Never in Mitosis gene A)-related kinase 8 (Nek8) are associated with a rare form of the juvenile renal cystic disease, nephronophthisis type 9, and mutations in murine Nek8 cause renal cysts in jck mice. Cystogenesis involves dysfunctional ciliary signaling, and we have previously reported that Nek8 localizes to the primary cilium in mouse kidney epithelial cells. We now report that in developing mouse kidney, Nek8 is detected in the cilia of a subset of ureteric-bud-derived tubules at embryonic day (E)15.5. An increasing proportion of ureteric-bud-derived tubules express ciliary Nek8 until E18.5. Postnatal day 1 and 7 Nek8 is observed with equal frequency in both ureteric-bud and non-ureteric-bud-derived tubules. To investigate the cell biological consequences of kinase-deficient and jck mutant forms of Nek8, we transiently expressed green fluorescent protein (GFP)-tagged constructs in vitro. Mutations in the kinase and C-terminal domains of Nek8 adversely affected ciliary targeting but did not affect ciliogenesis or ciliary length. Consistent with these in vitro observations, kidneys from homozygous jck mice revealed reduced ciliary expression of Nek8 compared with kidneys from heterozygous (unaff...Continue Reading

References

Feb 26, 1998·Current Topics in Developmental Biology·J A Davies, J B Bard
Apr 23, 1999·Developmental Dynamics : an Official Publication of the American Association of Anatomists·R GuillaumeM Trudel
Jan 5, 2000·Proceedings of the National Academy of Sciences of the United States of America·P UpadhyaJ E Barker
Apr 20, 2000·Journal of the American Society of Nephrology : JASN·Lukas FoggensteinerRichard Sandford
Sep 12, 2000·Current Opinion in Genetics & Development·A Schedl, N D Hastie
Mar 14, 2002·The American Journal of Pathology·Véronique ChauvetMarie-Claire Gubler
May 14, 2003·Trends in Cell Biology·Matthew J O'ConnellTony Hunter
Oct 7, 2004·Journal of the American Society of Nephrology : JASN·Gregory J Pazour
Feb 19, 2005·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·John J Bissler, Bradley P Dixon
Jul 12, 2005·Cell and Tissue Research·Jens NürnbergerAndreas Kribben
Nov 4, 2005·Journal of the American Society of Nephrology : JASN·Moe R MahjoubLynne M Quarmby
Nov 11, 2005·Journal of Cell Science·Lynne M Quarmby, Moe R Mahjoub
Dec 13, 2005·Nature Reviews. Genetics·Friedhelm Hildebrandt, Edgar Otto
Dec 13, 2005·Nature Genetics·Evelyne FischerMarco Pontoglio
Jul 7, 2006·Annual Review of Cell and Developmental Biology·Gregory R Dressler
Jul 11, 2006·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Lisa M Guay-Woodford
Aug 25, 2006·Journal of the American Society of Nephrology : JASN·Laurie A SmithOxana Ibraghimov-Beskrovnaya
Nov 24, 2006·Nature·Nikolay O BukanovOxana Ibraghimov-Beskrovnaya
Jan 18, 2008·Journal of the American Society of Nephrology : JASN·Edgar A OttoFriedhelm Hildebrandt

❮ Previous
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Citations

May 29, 2009·Nature Reviews. Nephrology·Maddalena Marasà, Jeffrey B Kopp
Dec 4, 2013·American Journal of Nephrology·Takahisa KimataKazunari Kaneko
Jun 6, 2008·BMC Cell Biology·Mark C White, Lynne M Quarmby
Mar 9, 2010·Cell Division·Richa SinghYogeshwer Shukla
Jul 18, 2009·Journal of the American Society of Nephrology : JASN·Elizabeth VergheseJames A Deane
Apr 9, 2011·Journal of the American Society of Nephrology : JASN·Hyungshin YimThomas Benjamin
Jan 1, 2013·Journal of the American Society of Nephrology : JASN·Danielle K ManningDavid R Beier
Feb 10, 2010·Expert Opinion on Investigational Drugs·Franck A Belibi, Charles L Edelstein
Dec 20, 2011·Differentiation; Research in Biological Diversity·Prachee Avasthi, Wallace F Marshall
Dec 18, 2012·Nephrology·James A DeaneSharon D Ricardo
Jul 22, 2014·Traffic·Kayalvizhi Madhivanan, Ruben Claudio Aguilar
Jun 5, 2015·Frontiers in Physiology·Omar Z AmeerJacqueline K Phillips
Oct 29, 2013·Organogenesis·Paraskevi Goggolidou
Apr 30, 2008·Biochimica Et Biophysica Acta·Ouadah HadjebiJose Luis Rosa
Feb 17, 2017·Biochemical Society Transactions·Vladislav KorobeynikovErica A Golemis
Apr 12, 2020·Cells·Anna Adamiok-Ostrowska, Agnieszka Piekiełko-Witkowska

❮ Previous
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