Functional Redundancy of the B9 Proteins and Nephrocystins in Caenorhabditis elegans Ciliogenesis

Journal Article · Tue Jan 01 04:00:00 EST 2008 · Molecular Biology of the Cell

DOI:https://doi.org/10.1091/mbc.E07-10-1070· OSTI ID:937150

Williams, Corey ^[1]; Winkelbauer, Marlene ^[2]; Schafer, Jenny ^[3]; Michaud, III, Edward J ^[4]; Yoder, Bradley ^[1]

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1. University of Alabama, Birmingham
2. Yale University
3. Vanderbilt University
4. ORNL

Meckel-Gruber syndrome (MKS), nephronophthisis (NPHP), and Joubert syndrome (JBTS) are a group of heterogeneous cystic kidney disorders with partially overlapping loci. Many of the proteins associated with these diseases interact and localize to cilia and/or basal bodies. One of these proteins is MKS1, which is disrupted in some MKS patients and contains a B9 motif of unknown function that is found in two other mammalian proteins, B9D2 and B9D1. Caenorhabditis elegans also has three B9 proteins: XBX-7 (MKS1), TZA-1 (B9D2), and TZA-2 (B9D1). Herein, we report that the C. elegans B9 proteins form a complex that localizes to the base of cilia. Mutations in the B9 genes do not overtly affect cilia formation unless they are in combination with a mutation in nph-1 or nph-4, the homologues of human genes (NPHP1 and NPHP4, respectively) that are mutated in some NPHP patients. Our data indicate that the B9 proteins function redundantly with the nephrocystins to regulate the formation and/or maintenance of cilia and dendrites in the amphid and phasmid ciliated sensory neurons. Together, these data suggest that the human homologues of the novel B9 genes B9D2 and B9D1 will be strong candidate loci for pathologies in human MKS, NPHP, and JBTS.

• Research Organization: Oak Ridge National Laboratory (ORNL); Mouse Genetics Research Facility
• Sponsoring Organization: ORNL LDRD Director's R&D; SC USDOE - Office of Science (SC)
• DOE Contract Number: AC05-00OR22725
• OSTI ID: 937150
• Journal Information: Molecular Biology of the Cell, Journal Name: Molecular Biology of the Cell Journal Issue: 5 Vol. 19
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
DENDRITES
DISEASES
FUNCTIONALS
GENES
KIDNEYS
MAINTENANCE
MUTATIONS
NERVE CELLS
PATIENTS
PROTEINS
REDUNDANCY