Polycystic kidney disease protein fibrocystin localizes to the mitotic spindle and regulates spindle bipolarity

Jingjing Zhang, Maoqing Wu, Shixuan Wang, Jagesh V. Shah, Patricia D. Wilson, Jing Zhou

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Autosomal recessive polycystic kidney disease (ARPKD) is a significant hereditary renal disease occurring in infancy and childhood, which presents with greatly enlarged echogenic kidneys, ultimately leading to renal insufficiency and end-stage renal disease. ARPKD is caused by mutations in a single gene PKHD1, which encodes fibrocystin/polyductin (FPC), a large single transmembrane protein generally known to be on the primary cilium, basal body and plasma membrane. Here, using our newly generated antibody raised against the entire C-terminal intracellular cytoplasmic domain (ICD) of FPC, as well as our previously well-characterized antibody against a peptide of ICD, we report for the first time that at least one isoform of FPC is localized to the centrosome and mitotic spindle of dividing cells in multiple cell lines, including MDCK, mIMCD3, LLCPK1, HEK293, RCTEC and HFCT cells. Using short-hairpin-mediated RNA interference, we show that the inhibition of FPC function in MDCK and mIMCD3 cells leads to centrosome amplification, chromosome lagging and multipolar spindle formation. Consistent with our in vitro findings, we also observed centrosome amplification in the kidneys from human ARPKD patients. These findings demonstrate a novel function of FPC in centrosome duplication and mitotic spindle assembly during cell division. We propose that mitotic defects due to FPC dysfunction contribute to cystogenesis in ARPKD.

Original languageEnglish (US)
Article numberddq233
Pages (from-to)3306-3319
Number of pages14
JournalHuman Molecular Genetics
Volume19
Issue number17
DOIs
StatePublished - Jun 16 2010
Externally publishedYes

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Autosomal Recessive Polycystic Kidney
Polycystic Kidney Diseases
Centrosome
Spindle Apparatus
Kidney
Proteins
Basal Bodies
Inborn Genetic Diseases
Madin Darby Canine Kidney Cells
Antibodies
Cilia
RNA Interference
Cell Division
Small Interfering RNA
Chronic Kidney Failure
Renal Insufficiency
Protein Isoforms
Chromosomes
Cell Membrane
Cell Line

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Polycystic kidney disease protein fibrocystin localizes to the mitotic spindle and regulates spindle bipolarity. / Zhang, Jingjing; Wu, Maoqing; Wang, Shixuan; Shah, Jagesh V.; Wilson, Patricia D.; Zhou, Jing.

In: Human Molecular Genetics, Vol. 19, No. 17, ddq233, 16.06.2010, p. 3306-3319.

Research output: Contribution to journalArticle

Zhang, Jingjing ; Wu, Maoqing ; Wang, Shixuan ; Shah, Jagesh V. ; Wilson, Patricia D. ; Zhou, Jing. / Polycystic kidney disease protein fibrocystin localizes to the mitotic spindle and regulates spindle bipolarity. In: Human Molecular Genetics. 2010 ; Vol. 19, No. 17. pp. 3306-3319.
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