ZFIN ID: ZDB-PUB-160222-3
Dynamin Binding Protein (Tuba) deficiency inhibits ciliogenesis and nephrogenesis in vitro and in vivo
Baek, J.I., Kwon, S.H., Zuo, X., Kwon, S.Y., Kim, S.H., Lipschutz, J.H.
Date: 2016
Source: The Journal of biological chemistry   291(16): 8632-43 (Journal)
Registered Authors: Kim, Seok-Hyung
Keywords: CDC42, cilia, guanine nucleotide exchange factor (GEF), kidney, membrane trafficking
MeSH Terms:
  • Animals
  • Cilia/genetics
  • Cilia/metabolism
  • Cytoskeletal Proteins/genetics
  • Cytoskeletal Proteins/metabolism*
  • Dogs
  • Gene Knockdown Techniques
  • Kidney/embryology*
  • Madin Darby Canine Kidney Cells
  • Mice
  • Organogenesis/physiology*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • cdc42 GTP-Binding Protein/genetics
  • cdc42 GTP-Binding Protein/metabolism
PubMed: 26895965 Full text @ J. Biol. Chem.
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ABSTRACT
Dysfunction of renal primary cilia leads to polycystic kidney disease (PKD). We previously showed that the exocyst, a protein trafficking complex, is essential for ciliogenesis, and is regulated by multiple Rho and Rab family GTPases, such as Cdc42. Cdc42 deficiency resulted in a disruption of renal ciliogenesis and a PKD phenotype in zebrafish and mice. Here we investigate the role of Tuba, a Cdc42-specific GEF, in ciliogenesis and nephrogenesis using Tuba knockdown MDCK cells, and tuba knockdown in zebrafish. Tuba depletion resulted in an absence of cilia, with impaired apical polarization and inhibition of hepatocyte growth factor (HGF)-induced tubulogenesis in Tuba knockdown MDCK cell cysts cultured in a collagen gel. In zebrafish, tuba was expressed in multiple ciliated organs, and, accordingly, tuba morphants showed various ciliary mutant phenotypes in these organs. Co-injection of tuba and cdc42 morpholinos at low doses, which alone had no effect, resulted in genetic synergy, and led to abnormal kidney development with highly disorganized pronephric duct cilia. Given the molecular nature of Cdc42 and Tuba, our data strongly suggest that tuba and cdc42 act in the same ciliogenesis pathway. Our study demonstrates that Tuba deficiency causes an abnormal renal ciliary and morphogenetic phenotype. Tuba most likely plays a critical role in ciliogenesis and nephrogenesis by regulating Cdc42 activity.
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