Nek8 mutation causes overexpression of galectin-1, sorcin, and vimentin and accumulation of the major urinary protein in renal cysts of jck mice

Nelly Valkova, Reem Yunis, Sally K. Mak, Kiandra Kang, Dietmar Kültz

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The jck murine model, which results from a double point mutation in the nek8 gene, has been used to study the mechanism of autosomal recessive polycystic kidney disease (ARPKD). The renal proteome of jck mice was characterized by two-dimensional gel electrophoresis combined with mass spectrometry (MALDI-TOF/TOF). Four newly identified proteins were found to accumulate in the kidneys of jck mice with polycystic kidney disease (PKD) compared with their wild-type littermates. The proteins galectin-1, sorcin, and vimentin were found to be induced 9-, 9-, and 25-fold, respectively, in the PKD proteome relative to the wild type. The identity of these proteins was established by peptide mass fingerprinting and de novo MS/MS sequencing of selected peptides. Up-regulation of these three proteins may be due to the nek8 mutation, and their function may be related to the signaling and structural processes in the primary cilium. Additionally a series of protein isoforms observed only in the ARPKD kidney was identified as the major urinary protein (MUP). Peptide sequencing demonstrated that the isoforms MUP1, MUP2, and MUP6 are contained in this series. The MUP series showed a number of male-specific isoforms and a phosphorylation of the entire series with an increasing degree of phosphorylation of the acidic isoforms. In addition, the MUP series was localized to the cyst fluid of PKD mice, and a cellular mislocalization of galectin-1, sorcin, and vimentin in PKD tubular epithelial cells was shown. The abnormal and extremely high accumulation of the MUPs in the ARPKD kidney may be linked to a defect in protein transport and secretion. The discovery of these proteins will provide new information on the molecular and cellular processes associated with the mechanism of ARPKD.

Original languageEnglish (US)
Pages (from-to)1009-1020
Number of pages12
JournalMolecular and Cellular Proteomics
Volume4
Issue number7
DOIs
StatePublished - Jul 2005

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Galectin 1
Autosomal Recessive Polycystic Kidney
Vimentin
Polycystic Kidney Diseases
Cysts
Kidney
Protein Isoforms
Mutation
Proteome
Proteins
Phosphorylation
Cyst Fluid
Peptides
Peptide Mapping
Cilia
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Electrophoresis, Gel, Two-Dimensional
Protein Transport
Point Mutation
Mass Spectrometry

ASJC Scopus subject areas

  • Biochemistry

Cite this

Nek8 mutation causes overexpression of galectin-1, sorcin, and vimentin and accumulation of the major urinary protein in renal cysts of jck mice. / Valkova, Nelly; Yunis, Reem; Mak, Sally K.; Kang, Kiandra; Kültz, Dietmar.

In: Molecular and Cellular Proteomics, Vol. 4, No. 7, 07.2005, p. 1009-1020.

Research output: Contribution to journalArticle

Valkova, Nelly ; Yunis, Reem ; Mak, Sally K. ; Kang, Kiandra ; Kültz, Dietmar. / Nek8 mutation causes overexpression of galectin-1, sorcin, and vimentin and accumulation of the major urinary protein in renal cysts of jck mice. In: Molecular and Cellular Proteomics. 2005 ; Vol. 4, No. 7. pp. 1009-1020.
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