𝔖 Bobbio Scriptorium
✦   LIBER   ✦

The biological activity of ubiquitinated BoNT/B light chain in vitro and in human SHSY-5Y neuronal cells

✍ Scribed by Xuerong Shi; Jennifer E. Curran; Zhilin Liao; Richard K. Gordon

Publisher
John Wiley and Sons
Year
2009
Tongue
English
Weight
213 KB
Volume
108
Category
Article
ISSN
0730-2312

No coin nor oath required. For personal study only.

✦ Synopsis

Abstract

BoNT/B light chain is a zinc‐dependent endopeptidase. After entering its target, the neuronal cell, BoNT/B is responsible for synaptobrevin‐2 (VAMP‐2) cleavage. This results in reduced neurotransmitter (acetylcholine) release from synaptic vesicles, yielding muscular paralysis. Since the toxin persists in neuronal cells for an extended period, regeneration of VAMP‐2 is prevented. We evaluated therapeutic targets to overcome botulinum persistence because early removal would rescue the neuronal cell. The ubiquitination/proteasome cellular pathway is responsible for removing “old” or undesirable proteins. Therefore, we assessed ubiquitination of BoNT/B light chain in vitro, and characterized the effects of ubiquitination modulating drugs, PMA (phorbol 12‐myristate 13‐acetate) and expoxomicin, on ubiquitination of BoNT/B light chain in neuronal cells. Both drugs altered BoNT/B light chain ubiquitination. Ubiquitination in vitro and in cells decreased the biological activity of BoNT/B light chain. These results further elucidate BoNT protein degradation pathways in intoxicated neuronal cells and mechanisms to enhance toxin removal. J. Cell. Biochem. 108: 660–667, 2009. Published 2009 Wiley‐Liss, Inc.

📜 SIMILAR VOLUMES

Un-nicked BoNT/B activity in human SHSY-
Un-nicked BoNT/B activity in human SHSY-5Y neuronal cells
✍ Xuerong Shi; Gregory E. Garcia; Madhusoodana P. Nambiar; Richard K. Gordon 📂 Article 📅 2008 🏛 John Wiley and Sons 🌐 English ⚖ 180 KB 👁 1 views

## Abstract BoNT/B holotoxin (HT) from the native source is a mixture of nicked and un‐nicked forms. A previous study showed that while un‐nicked HT could be transcytosed by intestinal epithelial cells, they did not correlate this with proteolytic activity or biological effect(s). Un‐nicked HT is l

TCEP treatment reduces proteolytic activ
TCEP treatment reduces proteolytic activity of BoNT/B in human neuronal SHSY-5Y cells
✍ Xuerong Shi; Gregory E. Garcia; Roger J. Neill; Richard K. Gordon 📂 Article 📅 2009 🏛 John Wiley and Sons 🌐 English ⚖ 296 KB 👁 1 views

## Abstract The light chain (LC) of botulinum neurotoxin B (BoNT/B) is unable to enter target neuronal cells by itself. It is brought into the cell in association with the BoNT/B heavy chain (HC) through endocytosis. The BoNT HC‐LC subunits are held together by a single disulfide bond. Intracellula