title: Requirement for a uroplakin 3a-like protein in the development of zebrafish pronephric tubule epithelial cell function, morphogenesis, and polarity.
abstract: Uroplakin (UP)3a is critical for urinary tract development and function; however, its role in these processes is unknown. We examined the function of the UP3a-like protein Upk3l, which was expressed at the apical surfaces of the epithelial cells that line the pronephric tubules (PTs) of the zebrafish pronephros. Embryos treated with upk3l-targeted morpholinos showed decreased pronephros function, which was attributed to defects in PT epithelial cell morphogenesis and polarization including: loss of an apical brush border and associated phospho-ERM proteins, apical redistribution of the basolateral Na(+)/K(+)-ATPase, and altered or diminished expression of the apical polarity complex proteins Prkcz (atypical protein kinase C zeta) and Pard3 (Par3). Upk3l missing its C-terminal cytoplasmic domain or containing mutations in conserved tyrosine or proline residues did not rescue, or only partially rescued the effects of Upk3l depletion. Our studies indicate that Upk3l promotes epithelial polarization and morphogenesis, likely by forming or stimulating interactions with cytoplasmic signaling or polarity proteins, and that defects in this process may underlie the pathology observed in UP3a knockout mice or patients with renal abnormalities that result from altered UP3a expression.
authors: Department of Medicine Renal-Electrolyte Division, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors: Shalini
authors: S
authors: Mitra
authors: Stefan
authors: S
authors: Lukianov
authors: Wily G
authors: WG
authors: Ruiz
authors: Chiara
authors: C
authors: Cianciolo Cosentino
authors: Subramaniam
authors: S
authors: Sanker
authors: Linton M
authors: LM
authors: Traub
authors: Neil A
authors: NA
authors: Hukriede
authors: Gerard
authors: G
authors: Apodaca
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016764:Cell Polarity; D004285:Dogs; D004489:Edema, Cardiac / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D007668:Kidney / Q000002:abnormalities; D007684:Kidney Tubules / Q000166:cytology* / Q000254:growth & development* / Q000502:physiology / Q000503:physiopathology; D051379:Mice; D008969:Molecular Sequence Data; D009024:Morphogenesis; D009154:Mutation; D017434:Protein Structure, Tertiary; D051381:Rats; D014564:Urogenital Abnormalities / Q000235:genetics; D060171:Uroplakin III / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000254:growth & development* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D060171:Uroplakin III; D029961:Zebrafish Proteins; C579541:upk3b protein, zebrafish