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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Lawrence, Gary W. Wang, Jiafu Brin, Mitchell F. Aoki, K. Roger Wheeler, Larry Dolly, J. Oliver |
| Description | Country affiliation: Ireland Author Affiliation: Lawrence GW ( International Centre for Neurotherapeutics, Dublin City University, Ireland.) |
| Abstract | Sympathetic neurons ramify to innervate multiple cells in target tissues. In compartmentalized cultures of rat superior cervical ganglion neurons, cleavage of synaptosomal-associated protein of Mr = 25 000 (SNAP-25) in neurites exposed to botulinum neurotoxin type A (BoNT/A) arrested their growth and collapsed interstitial branches, but this required large, nonclinical doses. A protease-inactive mutant proved ineffective, confirming involvement of SNAP-25 in neurite extension and arborization. BoNT/C1 acted like BoNT/A, but BoNT/E caused only mild inhibition, likely due to transient SNAP-25 proteolysis. Near-total lack of susceptibility to BoNT/B or BoNT/D revealed that vesicle-associated membrane protein (VAMPs) isoforms 1-3 are not essential. Neurite length was not reduced when either BoNT/A or BoNT/C1 was applied to the somata, with no detrimental effect on neuron viability being observed. Treatments that protect cells from deprivation of nerve growth factor failed to prevent the toxin-induced loss of neurites. Inactivation of SNAP-25 caused the accumulation at neurite branch sites of Golgi-derived organelles labelled with N-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-pentanoyl)-sphingosine conjugated to bovine serum albumin, prior to the collapse of arbors. Notably, neurite growth was ~ 1000-fold less susceptible to BoNT/A than cholinergic transmission in these neurons. Accordingly, a BoNT/A acceptor synaptic vesicle protein 2 (SV2) was found to be colocalized with VAMP 1-3, but not with VAMP 7, which is implicated in the growth of neurites. In conclusion, neurites depend on SNAP-25 for extension but this is quite resistant to BoNT/A, possibly, because of a low density of SV2 at growth sites that are distant from the highly susceptible regions of neurotransmitter release. |
| File Format | HTM / HTML |
| ISSN | 1742464X |
| Issue Number | 14 |
| Volume Number | 281 |
| e-ISSN | 17424658 |
| Journal | FEBS Journal |
| Language | English |
| Publisher | Wiley (on behalf of the Federation of European Biochemical Societies) |
| Publisher Date | 2014-07-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Biochemistry Golgi Apparatus Physiology Neurites Neurons Animals Botulinum Toxins Metabolism Botulinum Toxins, Type A Cells, Cultured Membrane Glycoproteins Nerve Tissue Proteins Cytology Rats Superior Cervical Ganglion Synaptic Transmission Synaptosomal-associated Protein 25 Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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