COPII-dependent export of cystic fibrosis transmembrane conductance regulator from the ER uses a di-acidic exit code
| Autor: | Ian A. Wilson, Jin San Yoo, Yu An, Sergei I. Bannykh, Bryan D. Moyer, Jeanne Matteson, William E. Balch, John R. Riordan, Xiaodong Wang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Models
Molecular Time Factors Mutant Vesicular Transport Proteins Cystic Fibrosis Transmembrane Conductance Regulator Vaccinia virus Endoplasmic Reticulum Transfection Article Protein Structure Secondary Cell Line 03 medical and health sciences 0302 clinical medicine Cricetinae Animals Humans Immunoprecipitation ΔF508 COPII Research Articles 030304 developmental biology 0303 health sciences biology Endoplasmic reticulum Temperature Membrane Proteins Proteins Cell Biology Transmembrane protein Cystic fibrosis transmembrane conductance regulator Cell biology Transport protein Protein Structure Tertiary Protein Transport Cyclic nucleotide-binding domain Mutation biology.protein COP-Coated Vesicles 030217 neurology & neurosurgery |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | Cystic fibrosis (CF) is a childhood hereditary disease in which the most common mutant form of the CF transmembrane conductance regulator (CFTR) ΔF508 fails to exit the endoplasmic reticulum (ER). Export of wild-type CFTR from the ER requires the coat complex II (COPII) machinery, as it is sensitive to Sar1 mutants that disrupt normal coat assembly and disassembly. In contrast, COPII is not used to deliver CFTR to ER-associated degradation. We find that exit of wild-type CFTR from the ER is blocked by mutation of a consensus di-acidic ER exit motif present in the first nucleotide binding domain. Mutation of the code disrupts interaction with the COPII coat selection complex Sec23/Sec24. We propose that the di-acidic exit code plays a key role in linking CFTR to the COPII coat machinery and is the primary defect responsible for CF in ΔF508-expressing patients. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|