Plasma membrane localization signals in the light chain of botulinum neurotoxin.

@article{citeulike:918540, abstract = {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.}, address = {Neurotoxin Research Program, Department of Biological Sciences, Allergan Inc., 2525 Dupont Drive, Irvine, CA 92612-1599, USA. fernandez\_ester@allergan.com}, author = {Fern\'{a}ndez-Salas, E. and Steward, L. E. and Ho, H. and Garay, P. E. and Sun, S. W. and Gilmore, M. A. and Ordas, J. V. and Wang, J. and Francis, J. and Aoki, K. R. }, citeulike-article-id = {918540}, comment = {Journal Club S\'{e}verine}, doi = {http://dx.doi.org/10.1073/pnas.0400229101}, issn = {0027-8424}, journal = {Proc Natl Acad Sci U S A}, keywords = {journal\_club}, month = {March}, number = {9}, pages = {3208--3213}, posted-at = {2006-10-30 15:18:03}, priority = {0}, title = {Plasma membrane localization signals in the light chain of botulinum neurotoxin.}, url = {http://dx.doi.org/10.1073/pnas.0400229101}, volume = {101}, year = {2004} }

TY - JOUR ID - citeulike:918540 L3 - citeulike-article-id:918540 TI - Plasma membrane localization signals in the light chain of botulinum neurotoxin. JF - Proc Natl Acad Sci U S A VL - 101 IS - 9 SP - 3208 EP - 3213 AD - Neurotoxin Research Program, Department of Biological Sciences, Allergan Inc., 2525 Dupont Drive, Irvine, CA 92612-1599, USA. fernandez_ester@allergan.com SN - 0027-8424 N2 - 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. KW - journal_club N1 - Journal Club Séverine AU - Fernández-Salas, E AU - Steward, LE AU - Ho, H AU - Garay, PE AU - Sun, SW AU - Gilmore, MA AU - Ordas, JV AU - Wang, J AU - Francis, J AU - Aoki, KR PY - 2004/03/02/ UR - http://dx.doi.org/10.1073/pnas.0400229101 ER -