Plasma membrane localization signals in the light chain of botulinum neurotoxin
| Autor: | Patton E. Garay, Ester Fernandez-Salas, Marcella A. Gilmore, Helen Ho, Sarah W. Sun, K. Roger Aoki, Lance E. Steward, Joanne Wang, Joseph V. Ordas, Joseph Francis |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Signal peptide
Botulinum Toxins Chromosomal Proteins Non-Histone Macromolecular Substances Blotting Western Nerve Tissue Proteins Biology Immunoglobulin light chain Transfection PC12 Cells Exocytosis Cell membrane Leucine medicine Animals Amino Acid Sequence Botulinum Toxins Type A Peptide sequence Multidisciplinary Binding Sites Cell Membrane SNAP25 Signal transducing adaptor protein Biological Sciences Subcellular localization Molecular biology Recombinant Proteins Cell biology Rats medicine.anatomical_structure Carrier Proteins |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 101(9) |
| ISSN: | 0027-8424 |
| Popis: | Botulinum neurotoxin (BoNT) is a potent biological substance used to treat neuromuscular and pain disorders. Both BoNT type A and BoNT type E display high-affinity uptake into motor neurons and inhibit exocytosis through cleavage of the synaptosome-associated protein of 25 kDa (SNAP25). The therapeutic effects of BoNT/A last from 3 to 12 months, whereas the effects of BoNT/E last less than 4 weeks. Using confocal microscopy and site-specific mutagenesis, we have determined that the protease domain of BoNT/A light chain (BoNT/A-LC) localizes in a punctate manner to the plasma membrane, colocalizing with the cleaved product, SNAP25 197 . In contrast, the short-duration BoNT/E serotype is cytoplasmic. Mutations in the BoNT/A-LC have revealed sequences at the N terminus necessary for plasma membrane localization, and an active dileucine motif in the C terminus that is likely involved in trafficking and interaction with adaptor proteins. These data support sequence-specific signals as determinants of intracellular localization and as a basis for the different durations of action in these two BoNT serotypes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|