Polarized apical sorting of guanylyl cyclase C is specified by a cytosolic signal. 2006

Caleb A Hodson, and Ilana G Ambrogi, and Robert O Scott, and Peter J Mohler, and Sharon L Milgram
Graduate Program in Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Receptor guanylyl cyclases respond to ligand stimulation by increasing intracellular cGMP, thereby initiating a variety of cell-signaling pathways. Furthermore, these proteins are differentially localized at the apical and basolateral membranes of epithelial cells. We have identified a region of 11 amino acids in the cytosolic COOH terminus of guanylyl cyclase C (GCC) required for normal apical localization in Madin-Darby canine kidney (MDCK) cells. These amino acids share no significant sequence homology with previously identified cytosolic apical sorting determinants. However, these amino acids are highly conserved and are sufficient to confer apical polarity to the interleukin-2 receptor alpha-chain (Tac). Additionally, we find two molecular weight species of GCC in lysates prepared from MDCK cells over-expressing GCC but observe only the fully mature species on the cell surface. Using pulse-chase analysis in polarized MDCK cells, we followed the generation of this mature species over time finding it to be detectable only at the apical cell surface. These data support the hypothesis that selective apical sorting can be determined using short, cytosolic amino acid motifs and argue for the existence of apical sorting machinery comparable with the machinery identified for basolateral protein traffic.

UI MeSH Term Description Entries
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D011993 Recombinant Fusion Proteins Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes. Fusion Proteins, Recombinant,Recombinant Chimeric Protein,Recombinant Fusion Protein,Recombinant Hybrid Protein,Chimeric Proteins, Recombinant,Hybrid Proteins, Recombinant,Recombinant Chimeric Proteins,Recombinant Hybrid Proteins,Chimeric Protein, Recombinant,Fusion Protein, Recombinant,Hybrid Protein, Recombinant,Protein, Recombinant Chimeric,Protein, Recombinant Fusion,Protein, Recombinant Hybrid,Proteins, Recombinant Chimeric,Proteins, Recombinant Fusion,Proteins, Recombinant Hybrid
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D003600 Cytosol Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components. Cytosols
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
D006162 Guanylate Cyclase An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. Guanyl Cyclase,Deoxyguanylate Cyclase,Guanylyl Cyclase,Inosinate Cyclase,Cyclase, Deoxyguanylate,Cyclase, Guanyl,Cyclase, Guanylate,Cyclase, Guanylyl,Cyclase, Inosinate
D000074261 Receptors, Enterotoxin Guanylate cyclase-coupled receptors that bind bacterial ENTEROTOXINS, as well as the endogenous peptides guanylin and uroguanylin. Ligand binding stimulates production of CYCLIC GMP by EPITHELIAL CELLS of the intestinal lumen, altering barrier permeability and mucus secretion. Mutations in the gene (GUCY2C) encoding this receptor are associated with some cases of hereditary diarrhea (Diarrhea 6) and MECONIUM ILEUS. Enterotoxin Receptor,Enterotoxin Receptors,Enterotoxin-Guanylin Receptor,Enterotoxin-Guanylin Receptors,GC-C Receptor,GC-C Receptors,Guanyl Cyclase-C Receptor,Guanyl Cyclase-C Receptors,Guanylin-Uroguanylin Receptor,Guanylin-Uroguanylin Receptors,Guanylyl Cyclase C,Heat-Stable Enterotoxin Receptor,Heat-Stable Enterotoxin Receptors,Receptor, Enterotoxin,Receptor, Guanyl Cyclase-C,Receptors, Guanyl Cyclase-C,Cyclase C, Guanylyl,Cyclase-C Receptors, Guanyl,Enterotoxin Guanylin Receptor,Enterotoxin Guanylin Receptors,Enterotoxin Receptor, Heat-Stable,Enterotoxin Receptors, Heat-Stable,GC C Receptor,GC C Receptors,Guanyl Cyclase C Receptor,Guanyl Cyclase C Receptors,Guanylin Uroguanylin Receptor,Guanylin Uroguanylin Receptors,Heat Stable Enterotoxin Receptor,Heat Stable Enterotoxin Receptors,Receptor, Enterotoxin-Guanylin,Receptor, GC-C,Receptor, Guanyl Cyclase C,Receptor, Guanylin-Uroguanylin,Receptor, Heat-Stable Enterotoxin,Receptors, Enterotoxin-Guanylin,Receptors, GC-C,Receptors, Guanyl Cyclase C,Receptors, Guanylin-Uroguanylin,Receptors, Heat-Stable Enterotoxin
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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