Functional polycystin-1 expression is developmentally regulated during epithelial morphogenesis in vitro: downregulation and loss of membrane localization during cystogenesis. 2002

Nikolay O Bukanov, and Hervé Husson, and William R Dackowski, and Brandon D Lawrence, and Patricia A Clow, and Bruce L Roberts, and Katherine W Klinger, and Oxana Ibraghimov-Beskrovnaya
Genzyme Corporation, 5 Mountain Road, Framingham, MA 01701-9322, USA.

Polycystin-1 is a protein mutated in the majority of cases of autosomal dominant polycystic kidney disease (ADPKD), but its role in the molecular pathway of tubulogenesis and cystogenesis is not understood. To define the role of polycystin-1 during dynamic changes in formation of intercellular contacts and cell polarity accompanying epithelial morphogenesis, we have utilized a 3D MDCK in vitro model of tubulogenesis and cystogenesis. Here we demonstrate that polycystin-1 is a novel component of desmosomal junctions of epithelial cells. A striking downregulation of polycystin-1 mRNA was detected in cysts as compared to tubules, leading to altered protein expression and localization. While polycystin-1 is localized to basolateral membranes of MDCK tubules, it is only detected in cytoplasmic pools in cystic cells. Furthermore, the expression of polycystin-1 is modulated during distinct stages of HGF-induced tubulogenesis from MDCK cysts. Thus, polycystin-1 is not detected in intercellular contacts at early steps of tubulogenesis, but assumes its basolateral localization at the time of cell polarization and lumen formation. An important role of polycystin-1 is further demonstrated using the pancreatic ductal epithelial cell line SU.86.86 which undergoes in vitro differentiation resulting in the formation of domes. Dome formation is thought to parallel tubular differentiation and morphogenesis in vivo. Our data reveal significant upregulation of polycystin-1 mRNA and protein levels in domes. Collectively, our results demonstrate a critical importance of controlled level of polycystin-1 expression for proper tubular differentiation and maturation. We suggest that the loss of polycystin-1 from its basolateral location in tubular epithelium may alter critical pathways controlling normal tubulogenesis leading to cystic transformation.

UI MeSH Term Description Entries
D007684 Kidney Tubules Long convoluted tubules in the nephrons. They collect filtrate from blood passing through the KIDNEY GLOMERULUS and process this filtrate into URINE. Each renal tubule consists of a BOWMAN CAPSULE; PROXIMAL KIDNEY TUBULE; LOOP OF HENLE; DISTAL KIDNEY TUBULE; and KIDNEY COLLECTING DUCT leading to the central cavity of the kidney (KIDNEY PELVIS) that connects to the URETER. Kidney Tubule,Tubule, Kidney,Tubules, Kidney
D009024 Morphogenesis The development of anatomical structures to create the form of a single- or multi-cell organism. Morphogenesis provides form changes of a part, parts, or the whole organism.
D010179 Pancreas A nodular organ in the ABDOMEN that contains a mixture of ENDOCRINE GLANDS and EXOCRINE GLANDS. The small endocrine portion consists of the ISLETS OF LANGERHANS secreting a number of hormones into the blood stream. The large exocrine portion (EXOCRINE PANCREAS) is a compound acinar gland that secretes several digestive enzymes into the pancreatic ductal system that empties into the DUODENUM.
D011506 Proteins Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein. Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D002462 Cell Membrane The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells. Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D004847 Epithelial Cells Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells. Adenomatous Epithelial Cells,Columnar Glandular Epithelial Cells,Cuboidal Glandular Epithelial Cells,Glandular Epithelial Cells,Squamous Cells,Squamous Epithelial Cells,Transitional Epithelial Cells,Adenomatous Epithelial Cell,Cell, Adenomatous Epithelial,Cell, Epithelial,Cell, Glandular Epithelial,Cell, Squamous,Cell, Squamous Epithelial,Cell, Transitional Epithelial,Cells, Adenomatous Epithelial,Cells, Epithelial,Cells, Glandular Epithelial,Cells, Squamous,Cells, Squamous Epithelial,Cells, Transitional Epithelial,Epithelial Cell,Epithelial Cell, Adenomatous,Epithelial Cell, Glandular,Epithelial Cell, Squamous,Epithelial Cell, Transitional,Epithelial Cells, Adenomatous,Epithelial Cells, Glandular,Epithelial Cells, Squamous,Epithelial Cells, Transitional,Glandular Epithelial Cell,Squamous Cell,Squamous Epithelial Cell,Transitional Epithelial Cell
D004848 Epithelium The layers of EPITHELIAL CELLS which cover the inner and outer surfaces of the cutaneous, mucus, and serous tissues and glands of the body. Mesothelium,Epithelial Tissue,Mesothelial Tissue,Epithelial Tissues,Mesothelial Tissues,Tissue, Epithelial,Tissue, Mesothelial,Tissues, Epithelial,Tissues, Mesothelial
D005455 Fluorescent Antibody Technique Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy. Antinuclear Antibody Test, Fluorescent,Coon's Technique,Fluorescent Antinuclear Antibody Test,Fluorescent Protein Tracing,Immunofluorescence Technique,Coon's Technic,Fluorescent Antibody Technic,Immunofluorescence,Immunofluorescence Technic,Antibody Technic, Fluorescent,Antibody Technics, Fluorescent,Antibody Technique, Fluorescent,Antibody Techniques, Fluorescent,Coon Technic,Coon Technique,Coons Technic,Coons Technique,Fluorescent Antibody Technics,Fluorescent Antibody Techniques,Fluorescent Protein Tracings,Immunofluorescence Technics,Immunofluorescence Techniques,Protein Tracing, Fluorescent,Protein Tracings, Fluorescent,Technic, Coon's,Technic, Fluorescent Antibody,Technic, Immunofluorescence,Technics, Fluorescent Antibody,Technics, Immunofluorescence,Technique, Coon's,Technique, Fluorescent Antibody,Technique, Immunofluorescence,Techniques, Fluorescent Antibody,Techniques, Immunofluorescence,Tracing, Fluorescent Protein,Tracings, Fluorescent Protein
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

Related Publications

Nikolay O Bukanov, and Hervé Husson, and William R Dackowski, and Brandon D Lawrence, and Patricia A Clow, and Bruce L Roberts, and Katherine W Klinger, and Oxana Ibraghimov-Beskrovnaya
July 1999, The American journal of physiology,
Nikolay O Bukanov, and Hervé Husson, and William R Dackowski, and Brandon D Lawrence, and Patricia A Clow, and Bruce L Roberts, and Katherine W Klinger, and Oxana Ibraghimov-Beskrovnaya
April 1997, The American journal of physiology,
Nikolay O Bukanov, and Hervé Husson, and William R Dackowski, and Brandon D Lawrence, and Patricia A Clow, and Bruce L Roberts, and Katherine W Klinger, and Oxana Ibraghimov-Beskrovnaya
August 1998, Journal of dental research,
Nikolay O Bukanov, and Hervé Husson, and William R Dackowski, and Brandon D Lawrence, and Patricia A Clow, and Bruce L Roberts, and Katherine W Klinger, and Oxana Ibraghimov-Beskrovnaya
January 2008, Development, growth & differentiation,
Nikolay O Bukanov, and Hervé Husson, and William R Dackowski, and Brandon D Lawrence, and Patricia A Clow, and Bruce L Roberts, and Katherine W Klinger, and Oxana Ibraghimov-Beskrovnaya
September 2003, Developmental dynamics : an official publication of the American Association of Anatomists,
Nikolay O Bukanov, and Hervé Husson, and William R Dackowski, and Brandon D Lawrence, and Patricia A Clow, and Bruce L Roberts, and Katherine W Klinger, and Oxana Ibraghimov-Beskrovnaya
April 2006, Proceedings of the National Academy of Sciences of the United States of America,
Nikolay O Bukanov, and Hervé Husson, and William R Dackowski, and Brandon D Lawrence, and Patricia A Clow, and Bruce L Roberts, and Katherine W Klinger, and Oxana Ibraghimov-Beskrovnaya
May 1997, The American journal of physiology,
Nikolay O Bukanov, and Hervé Husson, and William R Dackowski, and Brandon D Lawrence, and Patricia A Clow, and Bruce L Roberts, and Katherine W Klinger, and Oxana Ibraghimov-Beskrovnaya
September 2000, American journal of physiology. Gastrointestinal and liver physiology,
Nikolay O Bukanov, and Hervé Husson, and William R Dackowski, and Brandon D Lawrence, and Patricia A Clow, and Bruce L Roberts, and Katherine W Klinger, and Oxana Ibraghimov-Beskrovnaya
February 2007, Canadian journal of microbiology,
Nikolay O Bukanov, and Hervé Husson, and William R Dackowski, and Brandon D Lawrence, and Patricia A Clow, and Bruce L Roberts, and Katherine W Klinger, and Oxana Ibraghimov-Beskrovnaya
January 2014, PloS one,
Copied contents to your clipboard!