Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.69 (botulinum neurotoxin)
 1,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fusion of recycling and transcytotic vesicles with the apical and basolateral plasma membrane domains of Madin-Darby canine kidney (MDCK) cells requires the N-ethylmaleimide-sensitive factor and is sensitive to botulinum neurotoxin serotype E (BoNT/E). BoNT/E is thought to selectively proteolyze the 25,000-dalton synaptosomal associated protein (SNAP-25), a protein found in neurons or cells of neuroendocrine origin. However, SNAP-25 is not found in MDCK cells. One possible target for BoNT/E in MDCK cells is SNAP-23, a newly described SNAP-25 homolog that is found in several organs including kidney. Currently, the function of SNAP-23 is unknown. We have reconstituted transferrin recycling in permeabilized MDCK cells to assess the role of SNAP-23 in the endocytic traffic of this protein. We find that: (i) SNAP-23 is expressed in MDCK cells and is found both at the basolateral plasma membrane and associated with apical and basolateral vesicles, (ii) canine SNAP-23 is cleaved by BoNT/E, (iii) transferrin recycling is N-ethylmaleimide-sensitive factor-dependent and BoNT/E-sensitive, and (iv) addition of either exogenous SNAP-23 or anti-SNAP-23 antibodies inhibits ligand recycling. Our observations suggest that SNAP-23 may be required for fusion of recycling vesicles with the basolateral membrane of polarized MDCK cells.
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PMID:SNAP-23 requirement for transferrin recycling in Streptolysin-O-permeabilized Madin-Darby canine kidney cells. 965 73

Tetanus neurotoxin (TeNT) and botulinum neurotoxin (BoNT) are clostridial neurotoxins (CNTs) responsible for the paralytic diseases tetanus and botulism, respectively. CNTs are AB toxins with an N-terminal zinc-metalloprotease light chain that is linked by a disulfide bond to a C-terminal heavy chain that includes a translocation domain and a receptor-binding domain (HCR). Current models predict that the HCR defines how CNTs enter and traffic in neurons. Recent studies implicate that domains outside the HCR contribute to CNT trafficking in neurons. In the current study, a recombinant, full-length TeNT derivative, TeNT(RY), was engineered to analyze TeNT cell entry. TeNT(RY) was atoxic in a mouse challenge model. Using Neuro-2a cells, a mouse neuroblastoma cell line, TeNT HCR (HCR/T) and TeNT(RY) were found to bind gangliosides with similar affinities and specificities, consistent with the HCR domain containing receptor binding function. Temporal studies showed that HCR/T and TeNT(RY) entered Neuro-2a cells slower than the HCR of BoNT/A (HCR/A), transferrin, and cholera toxin B. Intracellular localization showed that neither HCR/T nor TeNT(RY) localized with HCR/A or synaptic vesicle protein 2, the protein receptor for HCR/A. HCR/T and TeNT(RY) exhibited only partial intracellular colocalization, indicating that regions outside the HCR contribute to the intracellular TeNT trafficking. TeNT may require this complex functional entry organization to target neurons in the central nervous system.
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PMID:Entry of a recombinant, full-length, atoxic tetanus neurotoxin into Neuro-2a cells. 2447