PTH-Induced Downregulation of the Type IIa Na/Pi-Cotransporter Is Independent of Known Endocytic Motifs
| Autor: | Jürg Biber, Nati Hernando, J Forgo, Heini Murer |
|---|---|
| Přispěvatelé: | University of Zurich, Murer, H |
| Rok vydání: | 2000 |
| Předmět: |
Recombinant Fusion Proteins
media_common.quotation_subject Amino Acid Motifs Green Fluorescent Proteins Endocytic cycle Down-Regulation Biology Sodium-Phosphate Cotransporter Proteins Type IIa Endocytosis 10052 Institute of Physiology Cell Line Downregulation and upregulation Animals Protein Isoforms Tyrosine Internalization media_common 2727 Nephrology Symporters Sodium-Phosphate Cotransporter Proteins Opossums General Medicine Molecular biology Rats Luminescent Proteins Membrane protein Biochemistry Parathyroid Hormone Nephrology Cytoplasm 570 Life sciences biology Indicators and Reagents Carrier Proteins Cotransporter hormones hormone substitutes and hormone antagonists |
| Zdroj: | Journal of the American Society of Nephrology. 11:1961-1968 |
| ISSN: | 1046-6673 |
| Popis: | Parathyroid hormone (PTH)-induced inhibition of renal proximal tubular Na/P(i) cotransport involves two consecutive steps: endocytosis followed by lysosomal degradation of the type IIa Na/P(i) cotransporter. Tyrosine-, dileucine-, and diacidic-based motifs are suggested to be involved in endocytosis and/or lysosomal targeting of different plasma membrane proteins. The rat type IIa cotransporter (NaPi2) contains two cytoplasmic tyrosine residues (Y) within sequences highly homologous to tyrosine-based motifs (GY(402)FAM and Y(509)RWF), three cytoplasmic dileucine (LL(101), LL(374), and LI(591)) and two cytoplasmic diacidic motifs (EE(81) and EE(616)). We studied the role of these motifs on the PTH-induced retrieval and lysosomal degradation of the NaPi2 cotransporter. To follow its trafficking in vivo, the NaPi2 protein was fused to the carboxyl-terminal end of the enhanced green fluorescence protein. This fusion did not impair the apical targeting or the PTH-induced endocytosis of the wild-type cotransporter when transfected in opossum kidney cells. Single and multiple Y and LL mutants retained the apical targeting and the PTH-induced degradation. Mutations of the diacidic motifs were also without effect. These data suggest that the above three motifs are not required for the PTH-induced internalization and/or degradation of the cotransporter. |
| Databáze: | OpenAIRE |
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