Overexpression of the Xenopus tight-junction protein claudin causes randomization of the left-right body axis.
This study presents Xenopus claudin (Xcla), a tight-junction protein that is abundantly expressed in eggs and neuroectodermal precursors during early development. It was isolated via a differential screen for mRNAs enriched in microsomes in the Xenopus blastula. The Xcla protein contains four transmembrane domains and a carboxy-terminal cytoplasmic region with a putative PDZ-binding site. We show that this PDZ-binding site of Xcla is critical for its correct localization on the cell membrane and that a truncated form leads to delocalization of the tight-junction protein ZO-1. Overexpression of Xcla causes changes in the cell adhesion properties of blastomeres and leads to visceral situs randomization. The results suggest that left-right axial patterning is very sensitive to changes in regulation of cell-cell interactions and implicate a tight-junction protein in the determination of left-right asymmetry.
Brizuela
B J
BJ
Howard Hughes Medical Institute and Department of Biological Chemistry, University of California at Los Angeles, Los Angeles, California, 90095-1662, USA.
Wessely
O
O
De Robertis
E M
EM
D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning; D002448:Cell Adhesion; D057167:Claudins; D003001:Cloning, Molecular; D004625:Embryo, Nonmammalian / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D007839:Functional Laterality; D017629:Gap Junctions / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008861:Microsomes / Q000378:metabolism; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D019108:Tight Junctions / Q000502:physiology*; D014158:Transcription, Genetic; D014981:Xenopus / Q000196:embryology* / Q000235:genetics; D029867:Xenopus Proteins
D057167:Claudins; D008565:Membrane Proteins; D012333:RNA, Messenger; D029867:Xenopus Proteins; C422906:claudin protein, Xenopus